APOPTOZİS

Yıl 2012, Cilt: 3 Sayı: 11, 26 - 37, 03.03.2015

Canan Kaya Yasemin Çalışkan Zafer Yönden

Öz

Apoptosis is main kind of programmed cell death. It is a way of getting rid of unnecessary and abnormal cells. Apoptozis is necessary and useful for life cyle and different from necrosis, which is cell death because of acute cell damage, by the way of killing cells in a series molecular pathways. For example during embriological differentiation of human fingers, apoptosis must be started to separate the fingers from each other. The differention of cell shape and metabolism at the time of apoptosis occurs as a result of several enzymatical procedures. Being smaller while dying by the apoptosis is not seen during necrosis. In every seconds one million cells are eliminated by apoptosis. Controlled balance is provided between mitosis and apoptosis. Apoptosis provides usefulness for organisms and also damages cancer cells. There are variety of methods which are detected to apoptosis. Apoptosis disorders can result in cancer, infections, neurodegenerative diseases, ischemic diseases and other possible related diseases. The parameter in the biochemical pathways of apoptosis can be targeted in the treatment of diseases which caused by apoptosis fewness or excess.

Anahtar Kelimeler

Apoptosis, Bcl 2, Bax, programmed cell death, ladder pattern

APOPTOZİS

Öz

Apoptozis veya Apoptoz, programlanmış hücre ölümünün ana tiplerinden biridir. Bu tip vücutta ihtiyaç duyulmayan veya anormalleşmiş hücrelerden kurtulmanın normal yoludur. Akut hücresel zarar sonucu olan hücre ölümü tipi nekrozdan farklı olarak apoptoz belirli bir moleküler işlemler serisinin (sırasının) sonunda hücrenin ölümünü sağlar ve aynı zamanda organizmanın yaşam döngüsü için gerekli ve yararlıdır. Örneğin gelişen bir embriyoda insan parmaklarının farklılaşması için parmaklar arasındaki hücrelerin apoptoz başlatması gerekir ki parmaklar birbirinden ayrılabilsin. Hücre ölümü sırasında meydana gelen pek çok hücresel ve şekilsel değişimler, bazı enzimlerin rol oynadığı birtakım süreçler neticesinde gelişir. Nekroz'dan farklı olarak, apoptozise uğrayan bir hücre küçülerek ölür. Her saniye yaklaşık bir milyon hücremiz apoptozisle vücuttan uzaklaştırılmaktadır. Yapım (mitozis) ile yıkım (apoptozis) arasında kontrollü bir denge vardır. Apoptoz kanser hücrelerinin zararına ve organizmanın yararına çalışır. Apoptozisi saptamak için çok çeşitli yöntemler geliştirilmiştir. Apoptoz bozuklukları kanser, enfeksiyon hastalıkları, nörodejeneratif hastalıklar, iskemik hastalıklar gibi pek çok hastalığa neden olmaktadır. Apoptoz azlığı ya da fazlalığının neden olabileceği hastalıklarda biyokimyasal yollarda yer alan her hangi bir etken tedavide hedef alınabilir.

Anahtar Kelimeler

Apoptozis, Bcl 2, Bax, programlı hücre ölümü, ladder pattern

Kaynakça

• 1. Alles A, Alley K, Barrett JC et al. Apoptosis: a general comment. FASEB J 1991; 5: 2127-8.
• 2. Pınarbaşı E. Apopitozis (Programlı Hücre Ölümü). Yıldırım A, Bardakçı F, Karataş M, Tanyolaç B (Editörler). Moleküler Biyoloji. 2. Baskı, Nobel Yayın Dağıtım. 2010:425-470.
• 3. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26: 239-57.
• 4. Raff MC. Social control on cell survival and cell death. Nature 1992; 356:397-400.
• 5. Wright SC, Wei QS, Kinder DH, Larrick JW. Biochemical pathways ofapoptosis; nicotinamide adenine dinucleotide-deficient cells are resistant to tumor necrosis factor or ultraviolet light activation of the 24-kd apoptotic protease and DNA fragmentation. J. Exp. Med. 1996;183:463-471.
• 6. Gavrieli Y, Sherman Y, Shmuel A, Sason B. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. The Journal of Cell Biology. 1992;119(3):493-501..
• 7. Ulukaya E.Apoptozis ders notları. Erişim: http://biyokimya.uludag.edu.tr/ apoptozisdersnotu, 04.05.2007.
• 8. Herrmann M, Kalden JR. Apoptosis and autoimmunity, Wiley-Vch Verlag GmbH & Co. KGaA, University of Erlangen-Nuremberg, Institute for Clinical Immunology, Weinheim, Germany. 2003.
• 9. Mcphie D L, Coopersmith R, Peralta AH, Chen Y, Ivins KJ, Manly SP, Kozlowski MR, Neve KA, Neve RL. DNA synthesis and neuronal apoptosis caused by familial alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. The Journal of Neuroscience. 2003;23(17):6914–6927.
• 10. Piret JP, Arnould T, Fuks B, Chatelain P, Remacle J, Michiels C.Caspase activation precedes PTP opening in TNF-a-induced apoptosis in L929 cells. Mitochondrion.2004;3: 261-278.
• 11. Spector MS, Destroyers S, Haepener DJ, Hengartner MO. Interaction between the C Elegans cell death regulators ced-9 and ced-4. Nature 1997; 385: 653-6.
• 12. Güneş HV. Moleküler Hücre Biyolojisi. İstanbul Tıp Kitabevi.2010
• 13. Krajewski S, Krajewska M, Ellerby LM, Welsh K, Xie Z, Deveraux QL, Salvesen GS, Bredesen DE, Rosenthal RE, Fiskum G, Reed JC. Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proc Natl Acad Sci, USA.1999;96: 5752- 5757.
• 14. Tsujimoto Y. Role of Bcl-2 family of proteins in apoptosis, apoptosomes or mitochondria? Genes Cell. 1998; 3: 697-707 15. Shi YA. Structural view of mitochondria mediated apoptosis. Nos Struct Biol. 2001; 8: 394-401.
• 16. Xue L, Borutaite V, Tolkovsky AM. Inhibition of mitochondrial permeability transition and release of cytochrome c by anti-apoptotic nucleoside analogues. Biochem Pharmacol 2002;64:441-9
• 17. Pan TQ, Atkinson TP, Makris CM, et al. ALPS (autoimmune lymphoproliferative syndrome) associated with a mutation in Fas-Ligand. In: Programs and Abstracts of the 14th Annual Conference on Clinical Immunology and 5th International Symposium on Clinical Immunology. Washington; DC; 1999. p. 44.
• 18. Bell BD, Leverrier S, Weist BM, Newton RH, Arechiga AF, Luhrs KA, Morrissette NS, Walsh CM. FADD and caspase-8 control the outcome of autophagic signalling in proliferating T cells. PNAS. 2008;105:16677-82.
• 19. Yu L, Lenardo MJ, Baehrecke EH. Autophagy and caspases. Cell Cycle 2004;3:1124- 6.
• 20. Qian W, Liu J, Jin J, Ni W, Xu W. Arsenic trioxide induces not only apoptosis but also autophagic cell death in leukemia cell lines via up-regulation of Beclin-1. Leuk Res 2007;31:329–39.
• 21. Hara MR, Snyder SH. Cell signaling and neuronal death. Annu Rev Pharmacol Toxicol. 2007;47:117-41.
• 22. Kanoh M, Takemura G, Misao J, Hayakawa Y, Aoyama T, Nishigaki K, Noda T, Fujiwara T, Fukuda K, Minatoguchi S, Fujiwara H. Significance of myocytes withpositive DNA in situ nick end-labeling (TUNEL) in hearts with dilated cardiomyopathy not apoptosis but DNA repair. Circulation.1999;99:2757-2764.
• 23. Stassi G. Detection of apoptosis in tissues, Apoptozis, hastalıklarla ilişkisi ve güncel belirleme yöntemleri kursu. Dokuz Eylül Üniversitesi Sağlık Bilimleri Enstitüsü, İzmir; 2006.
• 24. Kültürsay H, Kayıkçıoğlu M.Apoptozis ve Kardiyovasküler Hastalıklar. Anadolu Kardiyoloji Dergisi.2002;4:323-329.
• 25. Murray RK. Cancer, Cancer Genes and Growth Factors. Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s Biochemistry. Lange Medical Book. 1999.
• 26. Meng XW, Lee SH, Kaufmann SH. Apoptosis In The Treatment Of Cancer: A Promise Kept? Curr Opin Cell Biol 2006;18: 668-76.
• 27. Kaufmann SH, Gores GJ. Apoptosis In Cancer: Cause And Cure. Bioessays. 2000;22: 1007-17.
• 28. Fisher De. Apoptosis In Cancer Therapy: Crossing The Threshold. Cell. 1994;78:539- 42.
• 29. Fischer U, Schulze-Osthoff K. New approaches and therapeutics targeting apoptosis in disease. Pharmacol Rew 2005;57:187-215.
• 30. Green DG, Kroemer G. Pharmacological manipulation of cell death: clinical application in sight? J Clin İnvest 2005;115(10): 2610.