Apoptosis: Pogramlanmış hücre ölümleri

Normal gelişimin ve hastalıklarla bağlantılı patolojik durumların bir öğesi olarak ortaya çıkabilen "proglamlanmış hücre ölümleri" çok hücreli pek çok canlıda bulunmuştur. Programlanmış hücre ölümleri veya diğer adı ile apoptosis, belirli hücrelerin kendi ölümlerini, yani "intiharlarını", aldıkları sinyal sonucu aktive etmeleridir. Apoptosis nematodlardan memelilere kadar pek çok organizmanın hücre ve doku çeşidinde tanımlanmıştır. Apoptosis, nekrozdan farklı olarak, ölen hücrenin aktif katılımı ile meydana gelir. Yani, "intihar et" komutu alan hücre bu olayı gerçekleştirmek için bazı gen ürünleri (proteinler, enzimler) sentezler ve gerekli fizyolojik düzenlemeleri gerçekleştirir. Apoptosis'i gerçekleştiren genler hayvanlarda ve bitkilerde bulunmuştur. Bu genlerin bir kısmı apoptosis'de indükleyici bir kısmı bir inhibitor gibi davranır. Değişik organizmalardaki apoptosis ile bağlantılı genler arasında, DNA dizilimi açısından, benzerlik bulunması evrimsel açıdan canlılar arasında korunmuş ortak bir programlanmış hücre ölüm mekanizmalarının varlığını akla getirmiştir. Apoptosis'in canlılardaki rolü, hayvanlarda olduğu gibi normal gelişimle ilgili olabileceği gibi, bitkilerdeki "aşırı duyarlı tepkime"de olduğu gibi patojenlere karşı savunma mekanizması ile ilgili de olabilir.

Apoptosis: Programmed cell death

Programmed cell death" has been found in many multicellular organisms and occurs as a part of normal development as well as in pathological processes associated with some diseases. Programmed cell death, or apoptosis, is the process whereby certain cells are induced to activate their own death or cell suicide. Apoptosis has been described in a wide variety of cell and tissue types from nematodes to mammals. Apoptosis, unlike necrosis, is mediated by the active participation of dying cells. In another words, the dying cells synthesize certain proteins and enzymes to carry out the "suicide" process. The genes involved in apoptosis have been defined in animals as well as in plants. Some of these genes act as inducers while the others as inhibitors. It has been found that apoptosis related genes have high homology in terms of DNA sequences, suggesting the occurence of an evolutionarily preserved common programmed cell death mechanism among multicellular organisms. The possible role of apoptosis may be related to the regulation of normal development as in animals or it may be involved in defense responses against pathogens as in hypersensitive response (HR) in plants.

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1. Wyllie, A.H., Kerr, J.F.R. and Currie, A.R., Cell death: the significance of apoptosis. Int. Rev. Cyt. 68: 251-306, 1980.
2. Schwartz, L.M., Kosz, L. and Kay, B.K., Gene activation is required for developmentally programmed cell death. Proc. Natl. Acad. Sci. USA 87: 6594-698, 1990.
3. Osborne, B.A., Induction of genes during apoptosis: examples from the immune system. Seminars in Cancer Bio. 6: 27-33, 1995.
4. Bellamy, C.O.C., Malcomson, R.D.G., Harrison, D.J. and Wyllie, A.H., Cell death in health and disease: the biology and regulation of apoptosis. Seminar in Cancer Biol. 6: 3-16, 1995.
5. Ellis, R.E., Yuan, J. and Horvitz, H.R., Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 7: 663-698, 1991.
6. Plymale, D.R., Tang, D.S., Comardelle, A.M., Fermin, C.D., Lewis, D.E. and Garry, R.F., Both necrosis and apoptosis contribute to HIV-1 induced killing of CD4 cells. AIDS 13 (14): 1827-1839, 1999.
7. Mittler, R. and Lam, E., Sacrifice in the face of foes: pathogeninduced programmed cell death in plants. Trends in Microbiology 4: 10-15, 1996.
8. Vaux, D.L., Toward and understanding of the molecular mechanisms of physiological cell death. Proc. Natl. Acad. Sci. USA 90: 786-789, 1993.
9. Lee, S., Christakos, S. and Small, M.B., Apoptosis and signal transduction: clues to a molecular mechanism. Curr. Op. Cell Biol. 5: 286-291, 1993.
10. Raff, M.C., Social controls on cell survival and cell death. Cell 356: 397-400, 1992.
11. Bates, R.C., Buret, A., van Helden, D.F., Horton, M.A. and Burns, G.F., Apoptosis induced by inhibition of cellular contact. J. Cell Biol. 125: 403-415, 1994.
12. Arends, M.J., Morris, R.G. and Wyllie, A.H., Apoptosis: the role of the endonuclease. Am. J. Pathol. 130: 593-608, 1990.
13. Mittler, R. and Lam, E., Identification, characterization, and purification of a tobacco endonuclease activity induced upon HS cell death. The Plant Cell 7: 1951-1962, 1995.
14. Oppenheim, R.W., Prevette, D., Tytell, M. and Homma, S., Naturally occurring and induced neuronal death in the chick embryo in vivo requires protein and RNA synthesis: evidence for the role of cell death genes. Developmental Biol. 138: 104-113, 1990.
15. Beidler, D.R., Ahuja, D., Wicha, M.S. and Toogood, P.L., Inhibiton of protein synthesis by didemnin B is not sufficient to induce apoptosis in human mammary carcinoma (MCF7) cells. Biochem. Pharmacol. 58(6): 1067-1074, 1999.
16. Meredith, J.E., Fazeli, B. and Schwartz, M.A., The extracellular matrix as a cell survival factor. Mol. Biol. Cell 4: 953-961, 1993.
17. Ameisen, J.C., The origin of programmed cell death. Science 272: 1278-1279, 1996.
18. Ellis, H.M. and Horvitz, H.R., Genetic control of pcd in the nematode Caenorhabditis elegans. Cell 44: 817-829, 1986.
19. Vaux, D.L., Haecker, G. and Strasser, A., An evolutionary perspective on apoptosis. Cell 76: 777-779, 1994.
20. Hengartner, M.O., Ellis, R.E. and Horvitz, H.R., Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356: 494-499, 1992.
21. Takahashi, M., Saito, H., Okuyama, T., Miyashita, T., Kosuga, M., Sumisa, F., Yamada, M., Ebinuma, H. and Ishii, H., Overexpression of Bcl-2 protects human hepatoma cells from Fas-antibodymediated apoptosis. J. Hepatol. 31(2): 315-322, 1999.
22. Nunez, G. and Clarke, M.F., The Bcl-2 family of proteins: regulators of cell death and survival. Trends in Cell Biol. 4: 399- 403, 1994.
23. Hong, J.R., Hsu, Y.L. and Wu, J.L., Infectious pancreatic necrosis induces apoptosis due to down-regulation of survival factor MCL1 protein expression in a fish cell line. Virus Res. 63 (1-2): 75-83, 1999.
24. Torre, D., Zeroli, C., Speranza, F., Martegani, R., Fiori, G. and Airoldi, M., Serum levels of Fas/Apo-1 and Bcl-2 in children with HIV-1 infection. Scand. J. Infect. Dis. 30 (6): 565-568, 1998.
25. Hockenbery, D., Nunez, G., Milliman, C., Schrelber, R.D. and Korsmeyer, S: Y., Bcl-2 is an inner mitochondrial membrane protein that blocks pcd. Nature 348: 334-336, 1990.
26. Hengartner, M.O. and Horvitz, H.R., Programmed cell death in Caenorhabditis elegans. Curr. Opin. Genet. Dev. 4: 581-586, 1994.
27. Pennell, R.I. and Lamb, C., Programmed cell death in plants. Plant Cell 9: 1157-1168, 1997.
28. Yeung, E.C. and Meinke, D.W., Embryogenesis in angiosperms: development of the suspensor. Plant Cell 5: 1371-1381, 1993.
29. Caliskan, M., Temporal and spatial analysis or germin synthesis, PhD Thesis, University of Leeds, U.K., 1997.
30. Jones, A.M. and Dangl, J.L., Logjam at the styx: programmed cel death in plants. Trends in Plant Sci 1: 114-119, 1996.
31. Fukuda, H., redifferentiation of single mesophyll cells into tracheary elements. Int. J. Plant Sci. 155: 262-271, 1994.
32. Smart, C.M., Gene expression during leaf senescence. New Phytol. 126: 419-448, 1994.
33. Gan, S. and Amasino, R.M., Making sense of senescence: moleculer genetic regulation and manipulation of leaf senescence. Plant Physiol. 113: 313-319, 1997.
34. Grant, S., Genetics of sex determination in flowering plants. Dev. Genet. 15: 214-230, 1994.
35. Carrington, J.C., Kasschau, K.D., Mahajan, S.K. and Schaad, M.C., Cell-to-cell and long distance transport of viruses in plants. Plant Cell 8: 1669-1681, 1996.
36. Caliskan, M. and Cuming, A.C., Spatial specificity of H2O2 - generating oxalate oxidase gene expression during wheat embryo development. Plant Journal 15 (2): 165-171, 1998.
37. Thordal-Christensen, H., Zhang, Z., Wei, Y. and Collinge, D.B., Subcellular localization of H2O2 in plants. H2O2 accumulation in papillae and hypersensitive response during the barley-powdery mildew interaction. Plant J. 11 (6): 1187-1194, 1997.
38. Ross, A.F., Systemic acquired resistance induced by localized virus infections in plants. Virology 14: 340-358, 1961.
39. Dietrich, R.A., Delaney, T.P., Uknes, S.J., Ward, E.R., Ryals, J.A. and Dangl, J.L., Arabidopsis mutants simulating disease resistance response. Cell 77: 565-577, 1994.
40. Ward, E.R., Uknes, S.J., Williams, S.C., Dincher, S.S., Wiederhold, D.L., Alexander, D.C., Ahl-Goy, P., Metraux, J.-P. and Ryals, J.A., Coordinate gene activity in response to agents that induce systemic acquired resistance. Plant Cell 3: 1085-1094, 1991.
41. Greenberg, J.T., Guo, A., Klessig, D.F. and Ausubel, F.M., Programmed cell death in plants: a pathogen-triggered response activated coordinately with multiple defense functions. Cell 77: 551-563, 1994.
42. Wojtaszek, P., Oxidative burst: an early plant response to pathogen infection. Biochem. J. 322: 681-692, 1997.
43. Zhang, Z., Collinge, D.B. and Thordal-Christensen, H., Germin-like oxalate oxidase, a H2O2-producting enzyme, accumulates in barley attacked by the powder mildew fungus. Plant J. 8 (1): 139-145, 1995.