Programlı Hücre Ölümü; Apoptoz

Öz

Organizmada yaşam, belirli aşamalardan oluşmaktadır. Bunlar; doğum, canlılığın devamı olan üreme, yaşlanma ve nihayetinde ölümdür. Yaşamın bu şekilde devam edebilmesi için canlıyı oluşturan temel fonksiyonlar arasında bir denge vardır. Organizmada yeni hücreler oluşurken, var olan hücrelerin bir kısmı da hücre ölümü ile ortadan kaldırılmaktadır ve böylece ölüm ile yaşam arasındaki denge korunmaktadır. Fizyolojik ve patolojik durumlarda hücreyi ölüme götüren ve işleyişleri farklı olan iki mekanizma vardır, nekroz ve apoptoz. Apoptoz, programlı hücre ölümü olarak bilinen enerjiye bağımlı fizyolojik bir süreçtir. Apoptoz, embriyolojik gelişim ve erişkin dokuların devamlılığında kritik rol oynar. Programlı hücre ölümü organizmanın ihtiyaç duymadığı, biyolojik görevini tamamlamış ya da hasarlı hücreleri genetik düzeyde de kontrol ederek yok eden bir mekanizmadır. Apoptoz hızının bozulduğu, yavaşladığı veya arttığı durumlarda çeşitli hastalıklar ortaya çıkmaktadır. Apoptozu düzenleyen mekanizma, çeşitli proteinleri ve molekülleri içerir. Bu moleküllerin karşılıklı aktivasyonu apoptozun gerçekleşmesi için önemlidir. Bu derlemede, programlı hücre ölümünün nasıl gerçekleştiği, apoptotik yolaklara ait moleküler mekanizmaların neler olduğu ve apoptozun belirlenmesinde kullanılan çeşitli yöntemler genel hatlarıyla ifade edilmiştir.

Anahtar Kelimeler

• Apoptoz
• Bcl-2
• Kaspaz

Programmed Cell Death; Apoptosis

Öz

Life in an organism consists of specific stages. These are birth, fertility that is the continuation of life, aging, and eventually death. In order for life to continue in this way, there is a balance between the basic functions that forming the life. While new cells are formed in the organism, some of the existing cells are eliminated by cell death, thus maintaining the balance between death and life. In physiological and pathological conditions, there are two mechanisms that lead to cell death and differ in their functioning, necrosis and apoptosis. Apoptosis is an energy-dependent physiological process known as programmed cell death. Apoptosis plays a critical role in embryological development and continuity of adult tissues. Programmed cell death is a mechanism that destroys cells that the organism does not need, that have completed their biological task or that control and destroy damaged cells at the genetic level. Various diseases occur when the rate of apoptosis is impaired, slowed down or increased. The mechanism that regulates apoptosis involves various proteins and molecules. Mutual activation of these molecules is important for apoptosis to occur. In this review, how programmed cell death occurs, what are the molecular mechanisms of the pathways and various methods used in the determination of apoptosis are expressed in general terms.

Anahtar Kelimeler

• Apoptosis
• Bcl-2
• Caspase

Kaynakça

1. 1.Celepli S, Bigat İ, Celepli P, Karagin PH. Apoptoz ve apoptotik yolların gözden geçirilmesi. Ankara: Türkiye Bilimsel ve Teknik Araştırma Kurumu; 2020.
2. 2.Coşkun G, Özgür H. Apoptoz ve nekrozun moleküler mekanizması. Arşiv Kaynak Tarama Dergisi. 2001;20(3):145-14.
3. 3.Aykaç A, Cabadak H. Post-traumatic stress disorder: The importance of apoptosis. Clinical and Experimental Health Sciences. 2016;6(4): 173-5.
4. 4.Kerr JF, Wylie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239-19.
5. 5.Dağdeviren T. Peri-implantasyon döneminde sıçan endometriumunda Wnt-Β katenin yolağının Tcf, lef ve caspase-9 ekspresyonundaki rolü (Yüksek Lisans Tezi). Sivas: Sivas Cumhuriyet Üniversitesi; 2019.
6. 6.Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407: 770-6.
7. 7.Renehan AG, Booth C, Potten CS. What is apoptosis, and why is it important BMJ. 2001;322(7301):1536-3.
8. 8.Çalışkan, M. Apoptosis: Pogramlanmış Hücre Ölümleri. Turk J Zool. 200;24:31-6.

9. 9.Meier P, Finch A, Evan G. Apoptosis in development. Nature. 2000;407(12):796-6.
10. 10.Hutchins JB, Barger SW. Why neurons die: cell death in the nervous system. Anat Rec. 1998; 253: 79-12.
11. 11.Billig H, Furuta I, Hsueh AJ. Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinol 1993;133:2204-12.
12. 12. Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407: 770-6.
13. 13.Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281(5381): 1312-5.
14. 14.Ellis R, Yuan J, Horvitz H. Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 1991;7: 663-36
15. 15.Bellamy CO, Malcomson RD, Harrison DJ, Wyllie AH. Cell death in health and disease: the biology and regulation of apoptosis. Semin Cancer Biol. 1995;6 (1): 3-16.
16. 16.Denault J, Salvesen G. Caspases: keys in the ignition of cell death. Chem Rev. 2002; 102: 4489-12.
17. 17.Gillies, LA, Kuwana T. (2014). Apoptosis regulation at the mitochondrial outer membrane. Journal Of Cellular Biochemistry. 2014;115(4):632-9.
18. 18.Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002; 2:647–10.
19. 19.Liou AKF, Clark RS, Henshall DC, Yin XM, Chen J. To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: a review on the stress activated signaling pathways and apoptotic pathways. Prog Neurobiol. 2003; 69:103– 42.
20. 20.Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochemical Sciences, 2001;26(1): 61-6.
21. 21.Rzayev E. Deneysel Pentilentetrazol-Epilepside 4-Fenil Butirik Asitin Endoplazmik Retikulum Stres ve Apoptoz Üzerine Etkisi (Doktora Tezi). Samsun; Ondokuz Mayıs Üniversitesi; 2020.
22. 22.Adrain C, Martin SJ. The mitochondrial apoptosome: A killer unleashed by the cytochrome seas. Trends Biochem Sci. 2001;26:390-7.
23. 23.Spierings DC, De Vries EG, Vellenga E, et al. Tissue distribution of the death ligand trail and its receptors. J Histochem Cytochem. 2004;52(6): 821-11.
24. 24.Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsako-Poulou V, Ross AJ. Proapoptotic bax and bak: a requisite gateway to mitochondrial dysfunction and death. Science. 2001; 292(5517):727–4.
25. 25.Danial N, Korsmeyer S. Cell death: critical control points. Cell. 2004;116:205-15.
26. 26.Adimoolam S, Ford JM. P53 regulation of dna damage recognation during nucleotide excision repair. Dna Repair. 2003;2:947-8.
27. 27.Brooks LC, Gu W. Ubiquitination, phosphorilation and acetylation: The molecular basis for regulation. Current Opinion In Cell Biology. 2003;15:164-8.
28. 28.Latonen L, Laiho M. Cellular uv damage responses-functions of tumor supressor P53. Bba. 2005;1755:71-19.
29. 29.Vousden KH, Lu X. Live or let die: the cells response to P53. Nat Rev Cancer. 2002;2:594- 11.
30. 30.Oskay S. P53-/- Ve P53 +/+ Hct116 Kolon Kanser Hücre Serilerinde Radyasyonun Hücre Proliferasyonu ve Telomeraz Aktivitesi Üzerine Etkisi (Yüksek Lisans Tezi). Ankara: Ankara Üniversitesi; 2008.
31. 31.Yang JK. Death effecter domain for the assembly of death-inducing signaling complex. Apoptosis. 2015;20(2):235–9.
32. 32.Gökhan A, Kılıç KD, Gülle K, Uyanıkgil Y, Çavuşoğlu T. Apoptotik yolaklar ve hedefe yönelik tedaviler. Medical Journal of Suleyman Demirel University, 2020;27(4):565-9.
33. 33.Peter ME, Krammer PH. The Ccd95(Apo-1/Fas) disc and beyond. Cell Death Differ. 2003;10(1):26–10.
34. 34.Curtin JF, Cotter TG. Live and let die: regulatory mechanism in fas mediated apoptosis. Cell Signal. 2003;15:983-10.
35. 35.Boice A, Bouchier-Hayes L. Targeting apoptotic caspases in cancer. Biochim Biophys Acta Mol Cell Res. 2020;1867(6):118688.
36. 36.Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388- 3.
37. 37.Graham RK, Ehrnhoefer DE, Hayden MR. Caspase-6 and neurodegeneration. Trends Neurosci 2011;34:646-11.
38. 38.Peña-Blanco A, García-Sáez AJ. Bax, bak and beyond-mitochondrial performance in apoptosis. Febs J. 2018;285:416-31.
39. 39.Tinel A, Tschopp J. The piddosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science. 2004;304:843-6.
40. 40.Choo Z, Loh A, Chen Z. Destined to die: apoptosis and pediatric cancers. Cancers (Basel). 2019;11:1623.
41. 41.Tomatır AG. Apoptoz: programlı hücre ölümü. Türkiye Klinikleri Tıp Bilimleri Dergisi, 2003;23(6):499-10.
42. 42.Israels ED, Israels LG. The cell cycle. The Oncologist,2000;5(6):510-4.
43. 43.D’arcy M. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biology İnternational. 2019;43:582-11.
44. 44.Pfeffer CM, Singh AT. Apoptosis: a target for anticancer Therapy. Int J Mol Sci. 2018;19:448.
45. 45.Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495-22.
46. 46.Grilo AL, Mantalaris A. Apoptosis: a Mammalian cell bioprocessing perspective. Biotechnology Advances. 2019;37:459-17.
47. 47.Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of bcl-2 family proteins. Nat Rev Mol Cell Biol. 2019;20:175-19.
48. 48.Gurzov EN, Eizirik DL. Bcl-2 proteins in diabetes: mitochondrial pathways of Β-cell death and dysfunction. Trends Cell Biol. 2011;21(7):424–8.
49. 49.Du Toit A. Cell death: balance through a bivalent regulator. Nat Rev Mol Cell Biol. 2013;14:546.
50. 50.Cimmino A, Calin GA, Fabbri M, et al. Mir-15 and Mir-16 induce apoptosis by targeting Bcl2. Proc Natl Acad Sci Usa. 2005;102:13944-9.
51. 51.Shamas-Din A, Kale J, Leber B, et al. Mechanisms of action of bcl-2 family proteins. Cold Spring Harb Perspect Biol. 2013;5:A008714.
52. 52.Flores-Romero H, Garcia-Saez A. The incomplete puzzle of the Bcl2 proteins. Cells. 2019; 8:1176.