Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.
In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.
Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.
Citation: Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004
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Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines.
In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122.
Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.
Non-tuberculous mycobacteria (NTM)-induced nodules following botulinum toxin injections are increasingly being reported [1]–[3]. These infections often present as persistent nodules, which can be challenging to diagnose and manage [3]–[5]. This report presents a rare case of Mycobacterium chelonae-induced granulomatous nodules following botulinum toxin injections and includes a comprehensive review of the literature on NTM infections specifically related to botulinum toxin procedures. The aim is to highlight the importance of accurate diagnosis, appropriate antimicrobial therapy, and to provide an overview of reported cases to inform clinical practice.
A 35-year-old healthy male presented with multiple tender and painful nodules localized at injection sites on the forehead and periorbital areas. These nodules appeared three weeks after receiving Onabotulinum toxin injections from an untrusted provider. Initially, the patient was treated with oral steroids by his initial provider without any improvement. On examination, the nodules were tender and erythematous, confined to the injection sites, and no lymphadenopathy was observed (Figure 1a,b). Empiric antibiotic therapy with oral ciprofloxacin 500 mg twice daily and clindamycin 900 mg daily was initiated to cover potential bacterial infections. However, there was no improvement after three days of treatment. A biopsy was performed on the largest nodule. The specimen was sent for histopathology to rule out mycobacterial infection or sarcoidosis. Additional samples were sent for mycobacterial, bacterial, and fungal cultures, along with NTM PCR testing. Histopathological analysis revealed interstitial granulomatous inflammation with mild necrosis, indicative of a suppurative granuloma (Figure 1c). NTM PCR confirmed the presence of Mycobacterium chelonae. Antimicrobial susceptibility testing was performed, showing no resistance. Based on the diagnosis of NTM-induced granulomatous nodules, the patient was started on a combination therapy of oral clarithromycin 500 mg, levofloxacin 500 mg, and trimethoprim/sulfamethoxazole 160 mg/800 mg, all administered twice daily for six months. Significant improvement was noted six weeks into the therapy, with total remission observed at four months. At an eight-month follow-up, the patient showed no signs of relapse.
A comprehensive review of the literature identified eight reported cases of botulinum toxin-induced granulomatous nodules attributed to NTM infection. The key characteristics of these cases are summarized in Table 1.
The eight cases involved female patients with a mean age of 38 years. Six cases were associated with botulinum toxin injections for wrinkle treatment, while two cases were related to injections for masseter hypertrophy. The nodules typically appeared an average of 20 days post-injection and were characterized by painful, erythematous, and violaceous lesions, with some cases progressing to abscess formation [1]–[7].
Of the eight cases, six underwent biopsy, which revealed suppurative granulomas [1]–[4],[6],[7]. In the remaining two cases, a biopsy was not performed due to positive culture results [1],[2]. All isolated organisms were identified as NTM. Specifically, five cases were caused by Mycobacterium abscessus [2]–[5], one case by Mycobacterium immunogenum [7], and one case was culture and PCR-negative but treated empirically based on strong clinical and histological suspicion [6]. One case presented with acid-fast positive bacilli on histology, but the specific NTM species was not identified [1]. Notably, nodules caused by M. abscessus appeared between 4 to 10 days post-injection, while the nodule due to M. immunogenum emerged 3.5 months after the procedure [2]–[5],[7].
To date, no previous cases of M. chelonae associated with botulinum toxin-induced granulomatous nodules have been reported in the literature. The identification of this organism in our case thus represents the first documented instance of M. chelonae as an etiological agent in such a context.
| Study | Age & Sex | Toxin Source | Clinical Presentation | Histology | Organism | Treatment | Outcome |
| Li et al. | 39/F | NA | Painful nodules at injection sites 1 week later | Necrotic granuloma | M. abscessus (PCR) | Levofloxacin 500 mg BID, clarithromycin 500 mg BID (stopped in 1 week), surgical excision | NA |
| Thanasarnaksorn et al. | 42/F | Neuronox® | Tender nodules at all sites of injection 4 days later | Suppurative granuloma | Negative culture and PCR for NTM | Clarithromycin 500 mg/day, levofloxacin 500 mg/day for 6 months (empirically) | Major improvement at 6 weeks, full resolution at 6 months |
| Deng et al. | 53/F | NA | Painful nodules and abscesses at injection sites 10 days later | Suppurative granuloma | M. abscessus (culture) | Amikacin 200 mg, clarithromycin 500 mg, moxifloxacin 400 mg for 7 months | Full resolution after 7 months |
| Chen et al. | 32/F | Non-trusted source | Painful papules and nodules on all injection sites 1 week later | Suppurative granuloma | M. abscessus (culture) | Prednisone 30 mg/d, intravenous azithromycin, clarithromycin 250 mg BID, rifampicin 450 mg daily, ethambutol 250 mg TID for 3 months | Full resolution after 3 months with atrophic scars and PIH |
| Chen et al. | 34/F | Non-trusted source | Painful papules and nodules on lower jaw, malar, and temple region 10 days later | Biopsy not done | M. abscessus (culture) | Intralesional corticosteroids, oral penicillin, gentamicin, debridement, clarithromycin 250 mg BID, rifampicin 450 mg daily for nearly 6 months | Full resolution after 6 months with scarring and PIH |
| Yeon et al. | 34/F | Unknown source | Tender nodule over the left mandible after 3.5 months | Suppurative granuloma | M. immunogenum (culture) | Phenoxymethylpenicillin, clindamycin, clarithromycin 500 mg BID for 6 months | Full resolution |
| Saeb-Lima et al. | 45/F | NA | Tender nodules at points of injection 1 week later | Suppurative granuloma with acid-fast positive bacilli | Culture not done | Rifampicin, clarithromycin, azithromycin for 40 days | Full resolution with PIH |
| Ou et al. | 25/F | Unknown source | Painful nodules on cheeks 10 days later | Biopsy not done | M. abscessus (culture) | Azithromycin for 2 weeks, surgical excision, clarithromycin 300 mg for 6 months | Full resolution with dog-ear deformity after excision |
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In patients presenting with nodules after botulinum toxin injections, initial management can include oral antibiotics and topical treatments [8],[9]. It is crucial to avoid starting oral steroids empirically due to the high risk of infectious nodules compared to non-infectious ones. Biopsy remains the gold standard for determining the etiology of the nodule. If the nodule is found to be inflammatory, such as in sarcoidal nodules, systemic steroids along with immunosuppressive agents may be administered [8],[10]–[14]. However, if the histology shows suppurative or necrotic features, NTM infection should be ruled out using special stains, cultures, and PCR [9].
For infectious granulomas with positive NTM PCR or culture results, treatment should be tailored according to antibiotic sensitivity profiles. Since M. abscessus is the most frequently isolated organism and is known for its rapid growth and high resistance rates, combination therapy involving at least two antimicrobial agents is recommended for a duration of 4 to 6 months. Preferred treatments include a macrolide, such as clarithromycin, paired with agents like amikacin, levofloxacin, cefoxitin or tigecycline [15]–[17].
In the single case involving M. immunogenum, successful treatment was achieved with clarithromycin 500 mg twice daily for six months [7]. Antimicrobial therapy alone led to complete remission in five cases, though post-inflammatory hyperpigmentation (PIH) was noted in three instances [1],[2]. When antimicrobial therapy proved insufficient, surgical excision or debridement was performed in three cases, despite the higher risk of scarring associated with these procedures [2],[4],[5].
Given that negative cultures and PCR results are not uncommon in NTM infections, it is crucial to consider NTM infection as a potential cause of suppurative granulomas with negative test results. For cases with strong clinical and histological suspicion, multiple specimens should be tested through culture and PCR if initial tests are negative. Alternatively, empirical treatment can be initiated based on clinical and histological findings [15],[16]. This approach was exemplified by Thanasarnaksorn et al., who achieved full remission with a six-month regimen of clarithromycin and levofloxacin despite initial negative test results [6].
This case, along with the review of the literature on NTM infections following botulinum toxin injections, underscores the necessity for clinicians to consider NTM infections in patients presenting with persistent nodules post-procedure, particularly when initial treatments fail. This is the first reported case of M. chelonae as the etiological agent in such a context. To prevent such infections, it is crucial for patients to seek treatment from trusted and licensed providers who use authentic products and perform procedures in sterile environments.
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
| [1] |
Sharma A, Sharma L, Goyal R (2021) Molecular signaling pathways and essential metabolic elements in bone remodeling: An implication of therapeutic targets for bone diseases. Curr Drug Targets 22: 77-104. https://doi.org/10.2174/1389450121666200910160404 
|
| [2] |
Zaidi M (2007) Skeletal remodeling in health and disease. Nat Med 13: 791-801. https://doi.org/10.1038/nm1593
|
| [3] |
Khosla S, Riggs BL (2005) Pathophysiology of age-related bone loss and osteoporosis. Endocrin Metab Clin North Am 34: 1015-1030. https://doi.org/10.1016/j.ecl.2005.07.009
|
| [4] |
Marie PJ (2015) Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies. Cell Mol Life Sci 72: 1347-1361. https://doi.org/10.1007/s00018-014-1801-2
|
| [5] |
Kawai M, Modder UI, Khosla S, et al. (2011) Emerging therapeutic opportunities for skeletal restoration. Nat Rev Drug Discov 10: 141-156. https://doi.org/10.1038/nrd3299
|
| [6] |
Gether U (2000) Uncovering molecular mechanisms involved in activation of G protein-coupled receptors. Endocr Rev 21: 90-113. https://doi.org/10.1210/edrv.21.1.0390
|
| [7] |
Wu M, Deng L, Zhu G, et al. (2010) G Protein and its signaling pathway in bone development and disease. Front Biosci (Landmark Ed) 15: 957-985. https://doi.org/10.2741/3656
|
| [8] |
Bowler WB, Gallagher JA, Bilbe G (1998) G-protein coupled receptors in bone. Front Biosci 3: 769-780. https://doi.org/10.2741/a320
|
| [9] |
Conklin BR, Hsiao EC, Claeysen S, et al. (2008) Engineering GPCR signaling pathways with RASSLs. Nat Methods 5: 673-678. https://doi.org/10.1038/nmeth.1232
|
| [10] |
Saggio I, Remoli C, Spica E, et al. (2014) Constitutive expression of Gsα(R201C) in mice produces a heriTable, direct replica of human fibrous dysplasia bone pathology and demonstrates its natural history. J Bone Miner Res 29: 2357-2368. https://doi.org/10.1002/jbmr.2267
|
| [11] |
Remoli C, Michienzi S, Sacchetti B, et al. (2015) Osteoblast-specific expression of the fibrous dysplasia (FD)-causing mutation Gsα(R201C) produces a high bone mass phenotype but does not reproduce FD in the mouse. J Bone Miner Res 30: 1030-1043. https://doi.org/10.1002/jbmr.2425
|
| [12] | Daisy CS, Romanelli A, Checchi M, et al. (2022) Expression and localization of Phosphoinositide-specific Phospholipases C in cultured, differentiating and stimulated human osteoblasts. J Cell Signal 3: 44-61. https://doi.org/10.33696/Signaling.3.067 |
| [13] |
Berridge MJ, Irvine RF (1984) Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315-321. https://doi.org/10.1038/312315a0
|
| [14] |
Berridge MJ (1981) Phosphatidylinositol hydrolysis: a multifunctional transducing mechanism. Mol Cell Endocrinol 24: 115-140. https://doi.org/10.1016/0303-7207(81)90055-1
|
| [15] |
Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 1793: 933-940. https://doi.org/10.1016/j.bbamcr.2008.10.005
|
| [16] |
Tang X, Edwards EM, Holmes BB, et al. (2006) Role of phospholipase C and diacylglyceride lipase pathway in arachidonic acid release and acetylcholine-induced vascular relaxation in rabbit aorta. Am J Physiol Heart Circ Physiol 290: H37-H45. https://doi.org/10.1152/ajpheart.00491.2005
|
| [17] |
Suh PG, Park J, Manzoli L, et al. (2008) Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Rep 41: 415-434. https://doi.org/10.5483/bmbrep.2008.41.6.415
|
| [18] |
Mebarek S, Abousalham A, Magne D, et al. (2013) Phospholipases of mineralization competent cells and matrix vesicles: roles in physiological and pathological mineralizations. Int J Mol Sci 14: 5036-5129. https://doi.org/10.3390/ijms14035036
|
| [19] |
Bahk YY, Song H, Baek SH, et al. (1998) Localization of two forms of phospholipase C-beta1, a and b, in C6Bu-1 cells. Biochim Biophys Acta 1389: 76-80. https://doi.org/10.1016/S0005-2760(97)00128-8
|
| [20] |
Mao GF, Kunapuli SP, Koneti Rao A (2000) Evidence for two alternatively spliced forms of phospholipase C-beta2 in haematopoietic cells. Brit J Haematol 110: 402-408. https://doi.org/10.1046/j.1365-2141.2000.02201.x
|
| [21] |
Kim MJ, Min DS, Ryu SH, et al. (1998) A cytosolic, galphaq- and betagamma-insensitive splice variant of phospholipase C-beta4. J Biol Chem 273: 3618-3624. https://doi.org/10.1074/jbc.273.6.3618
|
| [22] |
Lee SB, Rhee SG (1996) Molecular cloning, splice variants, expression, and purification of phospholipase C-delta 4. J Biol Chem 271: 25-31. https://doi.org/10.1074/jbc.271.1.25
|
| [23] |
Sorli SC, Bunney TD, Sugden PH, et al. (2005) Signaling properties and expression in normal and tumor tissues of two phospholipase C epsilon splice variants. Oncogene 24: 90-100. https://doi.org/10.1038/sj.onc.1208168
|
| [24] |
Lo Vasco VR, Fabrizi C, Artico M, et al. (2007) Expression of phosphoinositide-specific phospholipase C isoenzymes in cultured astrocytes. J Cell Biochem 100: 952-959. https://doi.org/10.1002/jcb.21048
|
| [25] |
Lo Vasco VR, Pacini L, Di Raimo T (2011) Expression of phosphoinositide-specific phospholipase C isoforms in human umbilical vein endothelial cells. J Clin Pathol 64: 911-915. http://dx.doi.org/10.1136/jclinpath-2011-200096
|
| [26] |
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2012) Expression of Phosphoinositide-specific Phospholipase C enzymes in normal endometrium and in endometriosis. Fertil Steril 98: 410-414. https://doi.org/10.1016/j.fertnstert.2012.04.020
|
| [27] |
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2013) Expression of Phosphoinositide-specific phospholipase C enzymes in human osteosarcoma cell lines. J Cell Commun Signal 7: 141-150. https://doi.org/10.1007/s12079-013-0194-6
|
| [28] |
Fais P, Leopizzi M, Di Maio V, et al. (2019) Phosphoinositide-specific Phospholipase C in normal human liver and in alcohol abuse. J Cell Biochem 120: 7907-7917. https://doi.org/10.1002/jcb.28067
|
| [29] | Leopizzi M, Di Maio V, Della Rocca C, et al. (2020) Supernatants from human osteosarcoma cultured cell lines induce modifications in growth and differentiation of THP-1 cells and phosphoinositide-specific phospholipase C enzymes. Multidiscip Cancer Invest 4: 1-12. https://doi.org/10.30699/mci.4.4.430 |
| [30] |
Hwang JI, Kim HS, Lee JR, et al. (2005) The interaction of phospholipase C-beta3 with Shank2 regulates mGluR-mediated calcium signal. J Biol Chem 280: 12467-12473. https://doi.org/10.1074/jbc.M410740200
|
| [31] |
Bertagnolo V, Mazzoni M, Ricci D, et al. (1995) Identification of PI-PLC beta 1, gamma 1, and delta 1 in rat liver: subcellular distribution and relationship to inositol lipid nuclear signalling. Cell Signal 7: 669-678. https://doi.org/10.1016/0898-6568(95)00036-O
|
| [32] |
Nishida T, Huang TP, Seiyama A, et al. (1998) Endothelin A-receptor blockade worsens endotoxin-induced hepatic microcirculatory changes and necrosis. Gastroenterology 115: 412-420. https://doi.org/10.1016/s0016-5085(98)70208-2
|
| [33] | Lo Vasco VR, Fabrizi C, Fumagalli L, et al. (2010) Expression of phosphoinositide specific phospholipase C isoenzymes in cultured astrocytes activated after stimulation with Lipopolysaccharide. J Cell Biochem 109: 1006-1012. https://doi.org/10.1002/jcb.22480 |
| [34] |
Lo Vasco VR, Leopizzi M, Chiappetta C, et al. (2013) Lypopolysaccharide down-regulates the expression of selected phospholipase C genes in cultured endothelial cells. Inflammation 36: 862-868. https://doi.org/10.1007/s10753-013-9613-3
|
| [35] |
Lo Vasco VR, Leopizzi M, Puggioni C, et al. (2014) Neuropeptide Y significantly reduces the expression of PLCB2, PLCD1 and moderately decreases selected PLC genes in endothelial cells. Mol Cell Biochem 394: 43-52. https://doi.org/10.1007/s11010-014-2079-2
|
| [36] |
Lo Vasco VR, Leopizzi M, Puggioni C, et al. (2014) Fibroblast growth factor acts upon the transcription of phospholipase C genes in human umbilical vein endothelial cells. Mol Cell Biochem 388: 51-59. https://doi.org/10.1007/s11010-013-1898-x
|
| [37] |
Di Raimo T, Leopizzi M, Mangino G, et al. (2016) Different expression and subcellular localization of Phosphoinositide-specific Phospholipase C enzymes in differently polarized macrophages. J Cell Commun Signal 10: 283-293. https://doi.org/0.1007/s12079-016-0335-9
|
| [38] |
Lo Vasco VR, Fabrizi C, Panetta B, et al. (2010) Expression pattern and sub cellular distribution of Phosphoinositide specific Phospholipase C enzymes after treatment with U-73122 in rat astrocytoma cells. J Cell Biochem 110: 1005-1012. https://doi.org/10.1002/jcb.22614
|
| [39] |
Lo Vasco VR, Leopizzi M, Di Maio V, et al. (2016) U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C. Springerplus 5: 156. https://doi.org/10.1186/s40064-016-1768-6
|
| [40] |
Lo Vasco VR (2010) Signalling in the genomic era. J Cell Commun Signal 4: 115-117. https://doi.org/10.1007/s12079-010-0091-1
|
| [41] |
Urciuoli E, Leopizzi M, Di Maio V, et al. (2020) Phosphoinositide-specific phospholipase C isoforms are conveyed by osteosarcoma-derived extracellular vesicles. J Cell Commun Signal 14: 417-426. https://doi.org/10.1007/s12079-020-00571-6
|
| [42] | Bleasdale JE, Thakur NR, Gremban RS, et al. (1990) Selective inhibition of receptor-coupled phospholipase C dependent processes in human platelets and polymorphonuclear neutrophils. J Pharmacol Exp Ther 255: 756-768. |
| [43] |
Hellberg C, Molony L, Zheng L, et al. (1996) Ca2+ signalling mechanisms of the β2 integrin on neutrophils: involvement of phospholipase Cγ2 and Ins (1, 4, 5) P3. Biochem J 317: 403-409. https://doi.org/10.1042/bj3170403
|
| [44] |
Smallridge RC, Kiang JG, Gist ID, et al. (1992) U-73122, an aminosteroid phospholipase C antagonist, non-competitively inhibits thyrotropin-releasing hormone effects in GH3 rat pituitary cells. Endocrinology 131: 1883-1888. https://doi.org/10.1210/endo.131.4.1396332
|
| [45] |
Yang YR, Follo MY, Cocco L, et al. (2013) The physiological roles of primary phospholipase C. Adv Biol Regul 53: 232-241. https://doi.org/10.1016/j.jbior.2013.08.003
|
| [46] |
Ramazzotti G, Bavelloni A, Blalock W, et al. (2016) BMP-2 Induced Expression of PLCβ1 That is a Positive Regulator of Osteoblast Differentiation. J Cell Physiol 231: 623-629. https://doi.org/10.1002/jcp.25107
|
| [47] |
Rammler DH, Zaffaroni A (1967) Biological implications of DMSO based on a review of its chemical properties. Ann N Y Acad Sci 141: 13-23. https://doi.org/10.1111/j.1749-6632.1967.tb34861.x
|
| [48] |
Jacob SW, Herschler R (1986) Pharmacology of DMSO. Cryobiology 23: 14-27. https://doi.org/10.1016/0011-2240(86)90014-3
|
| [49] |
Li X, Majdi S, Dunevall J, et al. (2015) Quantitative measurement of transmitters in individual vesicles in the cytoplasm of single cells with nanotip electrodes. Angew Chem Int Ed Engl 54: 11978-11982. https://doi.org/10.1002/anie.201504839
|
| [50] |
Norwood TH, Zeigler CJ, Martin GM (1976) Dimethyl sulfoxide enhances polyethylene glycol-mediated somatic cell fusion. Somatic Cell Genet 2: 263-270. https://doi.org/10.1007/bf01538964
|
| [51] | Norwood TH, Zeigler CJ (1982) The use of dimethyl sulfoxide in mammalian cell fusion. Techniques in Somatic Cell Genetics . Boston: Springer. https://doi.org/10.1007/978-1-4684-4271-7_4 |
| [52] |
Santos NC, Figueira-Coelho J, Martins-Silva J, et al. (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65: 1035-1041. https://doi.org/10.1016/s0006-2952(03)00002-9
|
| [53] |
Spray DC, Campos de Carvalho AC, Mendez-Otero R (2010) Chemical induction of cardiac differentiation in p19 embryonal carcinoma stem cells. Stem Cells Dev 19: 403-412. https://doi.org/10.1089/scd.2009.0234
|
| [54] |
Galvao J, Davis B, Tilley M (2013) Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J 28: 1317-1330. https://doi.org/10.1096/fj.13-235440
|
| [55] |
Best BP (2015) Cryoprotectant toxicity: facts, issues, and questions. Rejuvenation Res 18: 422-36. https://doi.org/10.1089/rej.2014.1656
|
| [56] |
Majdi S, Najafinobar N, Dunevall J, et al. (2017) DMSO chemically alters cell membranes to slow exocytosis and increase the fraction of partial transmitter released. Chembiochem 18: 1898-1902. https://doi.org/10.1002/cbic.201700410
|
| [57] |
de Ménorval MA, Mir LM, Fernández ML, et al. (2012) Effects of dimethyl sulfoxide in cholesterol-containing lipid membranes: a comparative study of experiments in silico and with cells. PLoS One 7: e41733. https://doi.org/10.1371/journal.pone.0041733
|
| [58] |
Notman R, Noro M, O'Malley B, et al. (2006) Molecular basis for dimethylsulfoxide (DMSO) action on lipid membranes. J Am Chem Soc 128: 13982-13983. https://doi.org/10.1021/ja063363t
|
| [59] |
Gurtovenko AA, Anwar J (2007) Modulating the structure and properties of cell membranes: the molecular mechanism of action of dimethyl sulfoxide. J Phys Chem B 111: 10453-10460. https://doi.org/10.1021/jp073113e
|
| [60] |
Hughes ZE, Mark AE, Mancera RL (2012) Molecular dynamics simulations of the interactions of DMSO with DPPC and DOPC phospholipid membranes. J Phys Chem B 116: 11911-11923. https://doi.org/10.1021/jp3035538
|
| [61] |
Gironi B, Kahveci Z, McGill B, et al. (2020) Effect of DMSO on the mechanical and structural properties of mmodel and biological mmembranes. Biophys J 119: 274-286. https://doi.org/10.1016/j.bpj.2020.05.037
|
| [62] |
Vickers AE, Fisher RL (2004) Organ slices for the evaluation of human drug toxicity. Chem Biol Interact 150: 87-96. https://doi.org/10.1016/j.cbi.2004.09.005
|
| [63] |
Thomas MJ, Smith A, Head DH, et al. (2005) Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases. Eur J Immunol 35: 1283-1291. https://doi.org/10.1002/eji.200425634
|
| [64] |
Cenni B, Picard D (1999) Two compounds commonly used for phospholipase C inhibition activate the nuclear estrogen receptors. Biochem Biophys Res Commun 261: 340-344. https://doi.org/10.1006/bbrc.1999.1017
|
| [65] |
Feisst C, Albert D, Steinhilber D, et al. (2005) The aminosteroid phospholipase C antagonist U-73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1Hpyrrole-2,5-dione) potently inhibits human 5-lipoxygenase in vivo and in vitro. Mol Pharmacol 67: 1751-1757. https://doi.org/10.1124/mol.105.011007
|
| [66] |
Hughes S, Gibson WJ, Young JM (2000) The interaction of U-73122 with the histamine H-1 receptor: implications for the use of U-73122 in defining H-1 receptor-coupled signalling pathways. Naunyn Schmiedeberg's Arch Pharmacol 362: 555-558. https://doi.org/10.1007/s002100000326
|
| [67] |
Walker EM, Bispham JR, Hill SJ (1998) Nonselective effects of the putative phospholipase C inhibitor, U73122, on adenosine A(1) receptor-mediated signal transduction events in Chinese hamster ovary cells. Biochem Pharmacol 56: 1455-1462. https://doi.org/10.1016/s0006-2952(98)00256-1
|
| [68] |
Berven LA, Barritt GJ (1995) Evidence obtained using single hepatocytes for inhibition by the phospholipase-C inhibitor U73122 of store-operated Ca2+ inflow. Biochem Pharmacol 49: 1373-1379. https://doi.org/10.1016/0006-2952(95)00050-a
|
| [69] |
Pulcinelli FM, Gresele P, Bonuglia M, et al. (1998) Evidence for separate effects of U73122 on phospholipase C and calcium channels in human platelets. Biochem Pharmacol 56: 1481-1484. https://doi.org/10.1016/s0006-2952(98)00146-4
|
| [70] |
Boujard D, Anselme B, Cullin C, et al. (2014) Vesikulärer Transport. Zell- und Molekularbiologie im Überblick . Berlin: Springer Spektrum. https://doi.org/10.1007/978-3-642-41761-0
|
| [71] | Bray D (1992) Cell Movements: From Molecules to Motility. New York: Garland Publishing Inc. https://doi.org/10.4324/9780203833582 |
| [72] |
Chhabra ES, Higgs HN (2007) The many faces of actin: matching assembly factors with cellular structures. Nat Cell Biol 9: 1110-1121. https://doi.org/10.1038/ncb1007-1110
|
| [73] |
Lauffenburger DA, Horwitz FA (1996) Cell migration: a physically integrated molecular process. Cell 84: 359-369. https://doi.org/10.1016/s0092-8674(00)81280-5
|
| [74] |
Ridley AJ, Schwartz MA, Burridge K, et al. (2003) Cell migration: integrating signals from front to back. Science 302: 1704-1709. https://doi.org/10.1126/science.1092053
|
| [75] |
Pollard TD, Borisy GG (2003) Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453-465. https://doi.org/10.1016/s0092-8674(03)00120-x
|
| [76] |
Chan AY, Raft S, Bailly M, et al. (1998) EGF stimulates an increase in actin nucleation and filament number at the leading edge of the lamellipod in mammary adenocarcinoma cells. J Cell Sci 111: 199-211. https://doi.org/10.1242/jcs.111.2.199
|
| [77] |
Damsky CH, Ilić D (2002) Integrin signaling: it's where the action is. Curr Opin Cell Biol 14: 594-602. https://doi.org/10.1016/s0955-0674(02)00368-x
|
| [78] |
Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110: 673-687. https://doi.org/10.1016/s0092-8674(02)00971-6
|
| [79] |
Wells A (1999) EGF receptor. Int J Biochem Cell Biol 31: 637-643. https://doi.org/10.1016/s1357-2725(99)00015-1
|
| [80] |
DeMali KA, Wennerberg K, Burridge K (2003) Integrin signaling to the actin cytoskeleton. Curr Opin Cell Biol 15: 572-582. https://doi.org/10.1016/s0955-0674(03)00109-1
|
| [81] |
Aspenström P (1999) Effectors for the Rho GTPases. Curr Opin Cell Biol 11: 95-102. https://doi.org/10.1016/s0955-0674(99)80011-8
|
| [82] |
DeMali KA, Burridge K (2003) Coupling membrane protrusion and cell adhesion. J Cell Sci 116: 2389-2397. https://doi.org/10.1242/jcs.00605
|
| [83] |
Burridge K, Wennerberg K (2004) Rho and Rac take center stage. Cell 116: 167-179. https://doi.org/10.1016/s0092-8674(04)00003-0
|
| [84] |
Beningo KA, Dembo M, Kaverina I, et al. (2001) Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153: 881-888. https://doi.org/10.1083/jcb.153.4.881
|
| [85] |
Balaban NQ, Schwarz US, Riveline D, et al. (2001) Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3: 466-472. https://doi.org/10.1038/35074532
|
| [86] |
Abercrombie M (1980) The Croonian Lecture, 1978-The crawling movement of metazoan cells. Proc R Soc Lond, Ser B 207: 129-147. https://doi.org/10.1098/rspb.1980.0017
|
| [87] |
Hinz B, Alt W, Johnen C, et al. (1999) Quantifying lamella dynamics of cultured cells by SACED, a new computer-assisted motion analysis. Exp Cell Res 251: 234-243. https://doi.org/10.1006/excr.1999.4541
|
| [88] |
Araki N, Egami Y, Watanabe Y, et al. (2007) Phosphoinositide metabolism during membrane ruffling and macropinosome formation in EGF-stimulated A431 cells. Exp Cell Res 313: 1496-1507. https://doi.org/10.1016/j.yexcr.2007.02.012
|
| [89] |
Rilla K, Koistinen A (2015) Correlative light and electron microscopy reveals the HAS3-induced dorsal plasma membrane ruffles. Int J Cell Biol 2015: 769163. https://doi.org/10.1155/2015/769163
|
| [90] |
Hoon JL, Wong WK, Koh CG (2012) Functions and regulation of circular dorsal ruffles. Mol Cell Biol 32: 4246-4257. https://doi.org/10.1128/MCB.00551-12
|
| [91] |
Bernitt E, Döbereiner HG, Gov NS, et al. (2017) Fronts and waves of actin polymerization in a bistability-based mechanism of circular dorsal ruffles. Nat Commun 8: 15863. https://doi.org/10.1038/ncomms15863
|
| [92] |
Li G, D'Souza-Schorey C, Barbieri MA, et al. (1997) Uncoupling of membrane ruffling and pinocytosis during Ras signal transduction. J Biol Chem 272: 10337-10340. https://doi.org/10.1074/jbc.272.16.10337
|
| [93] |
Jones SJ, Boyde A (1976) Morphological changes of osteoblasts in vitro. Cell Tissue Res 166: 101-107. https://doi.org/10.1007/BF00215129
|
| [94] |
Lohmann CH, Schwartz Z, Köster G, et al. (2000) Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition. Biomaterials 21: 551-561. https://doi.org/10.1016/s0142-9612(99)00211-2
|
| [95] |
Sala G, Dituri F, Raimondi C, et al. (2008) PPhospholipase Cγ1 is required for metastasis development and progression. Cancer Res 68: 10187-10196. https://doi.org/10.1158/0008-5472.CAN-08-1181
|
| [96] | Barber MA, Welch HCE (2006) PI3K and RAC signaling in leukocyte and cancer cell migration. Bull Cancer 93: 10044-10052. |
| [97] |
Marée AF, Grieneisen VA, Edelstein-Keshet L (2012) How cells integrate complex stimuli: the effect of feedback from phosphoinositides and cell shape on cell polarization and motility. PLoS computational biology 8: e1002402. https://doi.org/10.1371/journal.pcbi.1002402
|
| [98] |
Razzini G, Berrie CP, Vignati S, et al. (2000) Novel functional PI 3-kinase antagonists inhibit cell growth and tumorigenicity in human cancer cell lines. FASEB J 14: 1179-1187. https://doi.org/10.1096/fasebj.14.9.1179
|
| [99] |
Baugher PJ, Krishnamoorthy L, Price JE (2005) Rac1 and Rac3 isoform activation is involved in the invasive and metastatic phenotype of human breast cancer cells. Breast Cancer Res 7: R965-R974. https://doi.org/10.1186/bcr1329
|
| [100] |
Takenawa T, Miki H (2001) WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J Cell Sci 114: 1801-1809. https://doi.org/10.1242/jcs.114.10.1801
|
| [101] |
Zhao B, Wang HB, Lu YJ, et al. (2011) Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles. Cell Res 21: 741-753. https://doi.org/10.1038/cr.2011.29
|
| [102] |
Illenberger D, Schwald F, Gierschik P (1997) Characterization and purification from bovine neutrophils of a soluble guanine-nucleotide-binding protein that mediates isozyme-specific stimulation of phospholipase C beta2. Eur J Biochem 246: 71-77. https://doi.org/10.1111/j.1432-1033.1997.t01-1-00071.x
|
| [103] |
Illenberger D, Schwald F, Pimmer D, et al. (1998) Stimulation of phospholipase C-β2 by the Rho GTPases Cdc42Hs and Rac1. EMBO J 17: 6241-6249. https://doi.org/10.1093/emboj/17.21.6241
|
| [104] |
Illenberger D, Walliser C, Strobel J, et al. (2003) Rac2 regulation of phospholipase C-β 2 activity and mode of membrane interactions in intact cells. J Biol Chem 278: 8645-8652. https://doi.org/10.1074/jbc.m211971200
|
| [105] |
Reid DW, Nicchitta CV (2015) Diversity and selectivity in mRNA translation on the endoplasmic reticulum. Nat Rev Mol Cell Biol 16: 221-231. https://doi.org/10.1038/nrm3958
|
| [106] |
Rapoport TA (2007) Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes. Nature 450: 663-669. https://doi.org/10.1038/nature06384
|
| [107] |
Braakman I, Hebert DN (2013) Protein folding in the endoplasmic reticulum. Cold Spring Harb Perspect Biol 5: a013201. https://doi.org/10.1101/cshperspect.a013201
|
| [108] |
Fagone P, Jackowski S (2009) Membrane phospholipid synthesis and endoplasmic reticulum function. J Lipid Res 50: S311-S316. https://doi.org/10.1194/jlr.R800049-JLR200
|
| [109] |
Hebert DN, Garman SC, Molinari M (2005) The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol 15: 364-370. https://doi.org/10.1016/j.tcb.2005.05.007
|
| [110] |
Clapham DE (2007) Calcium signaling. Cell 131: 1047-1058. https://doi.org/10.1016/j.cell.2007.11.028
|
| [111] |
Westrate LM, Lee JE, Prinz WA, et al. (2015) Form follows function: the importance of endoplasmic reticulum shape. Annu Rev Biochem 84: 791-811. https://doi.org/10.1146/annurev-biochem-072711-163501
|
| [112] |
Jan CH, Williams CC, Weissman JS (2014) Principles of ER cotranslational translocation revealed by proximity-specific ribosome profiling. Science 346: 1257521. https://doi.org/10.1126/science.1257521
|
| [113] |
Glick BS, Nakano A (2009) Membrane traffic within the Golgi apparatus. Annu Rev Cell Dev Biol 25: 113-132. https://doi.org/10.1146/annurev.cellbio.24.110707.175421
|
| [114] |
Appenzeller-Herzog C, Hauri HP (2006) The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function. J Cell Sci 119: 2173-2183. https://doi.org/10.1242/jcs.03019
|
| [115] |
Jaffe LF (1983) Sources of calcium in egg activation: a review and hypothesis. Dev Biol 99: 265-276. https://doi.org/10.1016/0012-1606(83)90276-2
|
| [116] |
Eisen A, Reynolds GT (1985) Source and sinks for the calcium released during fertilization of single sea urchin eggs. J Cell Biol 100: 1522-1527. https://doi.org/10.1083/jcb.100.5.1522
|
| [117] | Samtleben S, Jaepel J, Fecher C, et al. (2013) Direct imaging of ER calcium with targeted-esterase induced dye loading (TED). J Vis Exp 75: e50317. https://doi.org/10.3791/50317 |
| [118] |
Oude Weernink PA, Han L, Jakobs KH, et al. (2007) Dynamic phospholipid signaling by G protein-coupled receptors. Biochim Biophys Acta 1768: 888-900. https://doi.org/10.1016/j.bbamem.2006.09.012
|
| [119] |
Kanehara K, Yu CY, Cho Y, et al. (2015) Arabidopsis AtPLC2 is a primary phosphoinositide-specific phospholipase C in phosphoinositide metabolism and the endoplasmic reticulum stress response. PLoS Genet 11: e1005511. https://doi.org/10.1371/journal.pgen.1005511
|
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Figures(4) / Tables(3)
Matteo Corradini, Marta Checchi, Marzia Ferretti, Francesco Cavani, Carla Palumbo, Vincenza Rita Lo Vasco. Endoplasmic reticulum localization of phosphoinositide specific phospholipase C enzymes in U73122 cultured human osteoblasts[J]. AIMS Biophysics, 2023, 10(1): 25-49. doi: 10.3934/biophy.2023004
| Study | Age & Sex | Toxin Source | Clinical Presentation | Histology | Organism | Treatment | Outcome |
| Li et al. | 39/F | NA | Painful nodules at injection sites 1 week later | Necrotic granuloma | M. abscessus (PCR) | Levofloxacin 500 mg BID, clarithromycin 500 mg BID (stopped in 1 week), surgical excision | NA |
| Thanasarnaksorn et al. | 42/F | Neuronox® | Tender nodules at all sites of injection 4 days later | Suppurative granuloma | Negative culture and PCR for NTM | Clarithromycin 500 mg/day, levofloxacin 500 mg/day for 6 months (empirically) | Major improvement at 6 weeks, full resolution at 6 months |
| Deng et al. | 53/F | NA | Painful nodules and abscesses at injection sites 10 days later | Suppurative granuloma | M. abscessus (culture) | Amikacin 200 mg, clarithromycin 500 mg, moxifloxacin 400 mg for 7 months | Full resolution after 7 months |
| Chen et al. | 32/F | Non-trusted source | Painful papules and nodules on all injection sites 1 week later | Suppurative granuloma | M. abscessus (culture) | Prednisone 30 mg/d, intravenous azithromycin, clarithromycin 250 mg BID, rifampicin 450 mg daily, ethambutol 250 mg TID for 3 months | Full resolution after 3 months with atrophic scars and PIH |
| Chen et al. | 34/F | Non-trusted source | Painful papules and nodules on lower jaw, malar, and temple region 10 days later | Biopsy not done | M. abscessus (culture) | Intralesional corticosteroids, oral penicillin, gentamicin, debridement, clarithromycin 250 mg BID, rifampicin 450 mg daily for nearly 6 months | Full resolution after 6 months with scarring and PIH |
| Yeon et al. | 34/F | Unknown source | Tender nodule over the left mandible after 3.5 months | Suppurative granuloma | M. immunogenum (culture) | Phenoxymethylpenicillin, clindamycin, clarithromycin 500 mg BID for 6 months | Full resolution |
| Saeb-Lima et al. | 45/F | NA | Tender nodules at points of injection 1 week later | Suppurative granuloma with acid-fast positive bacilli | Culture not done | Rifampicin, clarithromycin, azithromycin for 40 days | Full resolution with PIH |
| Ou et al. | 25/F | Unknown source | Painful nodules on cheeks 10 days later | Biopsy not done | M. abscessus (culture) | Azithromycin for 2 weeks, surgical excision, clarithromycin 300 mg for 6 months | Full resolution with dog-ear deformity after excision |
DownLoad:
CSV
| Study | Age & Sex | Toxin Source | Clinical Presentation | Histology | Organism | Treatment | Outcome |
| Li et al. | 39/F | NA | Painful nodules at injection sites 1 week later | Necrotic granuloma | M. abscessus (PCR) | Levofloxacin 500 mg BID, clarithromycin 500 mg BID (stopped in 1 week), surgical excision | NA |
| Thanasarnaksorn et al. | 42/F | Neuronox® | Tender nodules at all sites of injection 4 days later | Suppurative granuloma | Negative culture and PCR for NTM | Clarithromycin 500 mg/day, levofloxacin 500 mg/day for 6 months (empirically) | Major improvement at 6 weeks, full resolution at 6 months |
| Deng et al. | 53/F | NA | Painful nodules and abscesses at injection sites 10 days later | Suppurative granuloma | M. abscessus (culture) | Amikacin 200 mg, clarithromycin 500 mg, moxifloxacin 400 mg for 7 months | Full resolution after 7 months |
| Chen et al. | 32/F | Non-trusted source | Painful papules and nodules on all injection sites 1 week later | Suppurative granuloma | M. abscessus (culture) | Prednisone 30 mg/d, intravenous azithromycin, clarithromycin 250 mg BID, rifampicin 450 mg daily, ethambutol 250 mg TID for 3 months | Full resolution after 3 months with atrophic scars and PIH |
| Chen et al. | 34/F | Non-trusted source | Painful papules and nodules on lower jaw, malar, and temple region 10 days later | Biopsy not done | M. abscessus (culture) | Intralesional corticosteroids, oral penicillin, gentamicin, debridement, clarithromycin 250 mg BID, rifampicin 450 mg daily for nearly 6 months | Full resolution after 6 months with scarring and PIH |
| Yeon et al. | 34/F | Unknown source | Tender nodule over the left mandible after 3.5 months | Suppurative granuloma | M. immunogenum (culture) | Phenoxymethylpenicillin, clindamycin, clarithromycin 500 mg BID for 6 months | Full resolution |
| Saeb-Lima et al. | 45/F | NA | Tender nodules at points of injection 1 week later | Suppurative granuloma with acid-fast positive bacilli | Culture not done | Rifampicin, clarithromycin, azithromycin for 40 days | Full resolution with PIH |
| Ou et al. | 25/F | Unknown source | Painful nodules on cheeks 10 days later | Biopsy not done | M. abscessus (culture) | Azithromycin for 2 weeks, surgical excision, clarithromycin 300 mg for 6 months | Full resolution with dog-ear deformity after excision |
