Abstract
We previously showed that mycoplasmal infection effectively prevented apoptosis of infected cells, whereas other researchers have indicated that mycoplasmal infection promoted apoptosis. To understand the mechanism underlying this discrepancy, five different species of mycoplasmas were investigated for their effects on apoptosis of interleukin (IL)-3–dependent 32D cells. Results revealed that Mycoplasma fermentans and M. penetrans effectively supported continuous growth of 32D cells after IL-3 withdrawal. M. fermentans was more potent than M. penetrans. This effect was achieved by way of preventing apoptosis and stimulating cell proliferation. On the contrary, M. hominis and M. salivarium accelerated apoptosis of 32D cells. M. genitalium had no significant effect on apoptosis. The RNase protection assay indicated that the proapoptotic and antiapoptotic mycoplasmas altered the expression of major apoptosis regulatory genes differently. The difference in apoptosis regulatory gene expression induced by different species of mycoplasmas might be accountable for their effects on host cell apoptosis.
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Literature Cited
Ben-Menachem G, Mousa A, Brenner T, Pinto F, Zahringer U, Rottem S (2001) Choline deficiency induced by Mycoplasma fermentans enhances apoptosis of rat astrocytes. FEMS Microbiol Lett 201:157–162
Bendjennat M, Blanchard A, Loutfi M, Montagnier L, Bahraoui E (1999) Role of Mycoplasma penetrans endonuclease P40 as a potential pathogenic determinant. Infect Immun 67:4456–4462
Buzanska L, Zablocka B, Dybel A, Domanska-Janik K, Albrecht J (2000) Delayed induction of apoptosis by ammonia in C6 glioma cells. Neurochem Int 37:287–297
Compton MM (1992) A biochemical hallmark of apoptosis: Internucleosomal degradation of the genome. Cancer Metastasis Rev 11:105–119
Dedieu L, Chapey E, Balcer-Rodrigues V (2005) Mycoplasma mycoides ssp. mycoides biotype small colony-secreted components induce apoptotic cell death in bovine leucocytes. Scand J Immunol 62:528–538
Facchini LM, Penn LZ (1998) The molecular role of Myc in growth and transformation: Recent discoveries lead to new insights. FASEB J 12:633–651
Feng SH, Tsai S, Rodriguez J, Lo SC (1999) Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells. Mol Cell Biol 19:7995–8002
Gong H, Zolzer F, von Recklinghausen G, Rossler J, Breit S, Havers W, et al. (1999) Arginine deiminase inhibits cell proliferation by arresting cell cycle and inducing apoptosis. Biochem Biophys Res Commun 261:10–14
Greenberger JS, Sakakeeny MA, Humphries RK, Eaves CJ, Eckner RJ (1983) Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A 80:2931–2935
Hall RE, Agarwal S, Kestler DP (2000) Induction of leukemia cell differentiation and apoptosis by recombinant P48, a modulin derived from Mycoplasma fermentans. Biochem Biophys Res Commun 269:284–289
Hunt ME, Brown DR (2005) Mycoplasma alligatoris infection promotes CD95 (FasR) expression and apoptosis of primary cardiac fibroblasts. Clin Diagn Lab Immunol 12:1370–1377
Into T, Kiura K, Yasuda M, Kataoka H, Inoue N, Hasebe A, et al. (2004) Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappa B activation. Cell Microbiol 6:187–199
Komada Y, Zhang XL, Zhou YW, Ido M, Azuma E (1997) Apoptotic cell death of human T lymphoblastoid cells induced by arginine deiminase. Int J Hematol 65:129–141
Laneuville P, Timm M, Hudson AT (1994) bcr/abl expression in 32D cl3(G) cells inhibits apoptosis induced by protein tyrosine kinase inhibitors. Cancer Res 54:1360–1366
Lee JC, Hapel AJ, Ihle JN (1982) Constitutive production of a unique lymphokine (IL 3) by the WEHI-3 cell line. J Immunol 128:2393–2398
Li YH, Chen M, Brauner A, Zheng C, Skov Jensen J, Tullus K (2002) Ureaplasma urealyticum induces apoptosis in human lung epithelial cells and macrophages. Biol Neonate 82:166–173
Lo SC, Hayes MM, Tully JG, Wang RY, Kotani H, Pierce PF, et al. (1992) Mycoplasma penetrans sp. nov., from the urogenital tract of patients with AIDS. Int J Syst Bacteriol 42:357–364
Lo SC, Shih JW, Newton PBD, Wong DM, Hayes MM, Benish JR, et al. (1989) Virus-like infectious agent (VLIA) is a novel pathogenic mycoplasma: Mycoplasma incognitus. Am J Trop Med Hyg 41:586–600
Maniloff J, McElhaney RN, Flinch LR, Baseman JB (1992) Mycoplasmas, molecular biology, pathogenesis. Washington DC, American Society for Microbiology
Mesner PW, Winters TR, Green SH (1992) Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 119:1669–1680
Nunez G, London L, Hockenbery D, Alexander M, McKearn JP, Korsmeyer SJ (1990) Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol 144:3602–3610
Paddenberg R, Weber A, Wulf S, Mannherz HG (1998) Mycoplasma nucleases able to induce internucleosomal DNA degradation in cultured cells possess many characteristics of eukaryotic apoptotic nucleases. Cell Death Diff 5:517–528
Paddenberg R, Wulf S, Weber A, Heimann P, Beck LA, Mannherz HG (1996) Internucleosomal DNA fragmentation in cultured cells under conditions reported to induce apoptosis may be caused by mycoplasma endonucleases. Eur J Cell Biol 71:105–119
Raff MC (1992) Social controls on cell survival and cell death. Nature 356:397–400
Shibata K, Watanabe T (1997) Mycoplasma fermentans enhances concanavalin A-induced apoptosis of mouse splenic T cells. FEMS Immunol Med Microbiol 17:103–109
Sokolova IA, Vaughan AT, Khodarev NN (1998) Mycoplasma infection can sensitize host cells to apoptosis through contribution of apoptotic-like endonuclease(s). Immunol Cell Biol 76:526–534
Thatte HS, Rhee JH, Zagarins SE, Treanor PR, Birjiniuk V, Crittenden MD, et al. (2004) Acidosis-induced apoptosis in human and porcine heart. Ann Thorac Surg 77:1376–1383
Tsai S, Wear DJ, Shih JW, Lo SC (1995) Mycoplasmas and oncogenesis: Persistent infection and multistage malignant transformation. Proc Natl Acad Sci U S A 92:10197–10201
Tully JG (1983) The Emmy Klieneberger-Nobel Award lecture. Reflections on recovery of some fastidious mollicutes with implications of the changing host patterns of these organisms. Yale J Biol Med 56:799–813
Vanden Bush TJ, Rosenbusch RF (2002) Mycoplasma bovis induces apoptosis of bovine lymphocytes. FEMS Immunol Med Microbiol 32:97–103
Wyllie AH (1992) Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: An overview. Cancer Metastasis Rev 11:95–103
Zhang S, Tsai S, Lo SC (2006) Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation. BMC Cancer 6:116
Zhang S, Wear DJ, Lo S (2000) Mycoplasmal infections alter gene expression in cultured human prostatic and cervical epithelial cells. FEMS Immunol Med Microbiol 27:43–50
Acknowledgments
We are grateful to Tamara Newsome and Joe F. Rodriguez for their critical reviews of this manuscript. This work was supported by grants (UBUY, UBPA, UBIM, and UBZZ) from American Registry of Pathology/Armed Forces Institute of Pathology.
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Zhang, S., Lo, SC. Effect of Mycoplasmas on Apoptosis of 32D Cells Is Species-Dependent. Curr Microbiol 54, 388–395 (2007). https://doi.org/10.1007/s00284-006-0491-x
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DOI: https://doi.org/10.1007/s00284-006-0491-x