FIND ARTICLE

Volume: 
Issue: 
2
Date of issue: 

Most of the currently used anticancer drugs and radiotherapy induces apoptosis by DNA damage or inhibition of key enzymes involved in cell survival signaling pathways . This triggers a cascade of reactions leading to the activation of pro-apoptotic proteins Bcl- 2 family , such as Bad , Bid , Bax or Bak , forming a specific channel or coformation of megachannels ( mPTP ) in the outer mitochondrial membrane , allow the release of apoptogenic proteins , such as cytochrome c , Smac / DIABLO , AIF , Omi/HtrA2 , procaspase 9 and 3 and endonuclease G. Smac / DIABLO (second mitochondria -derived activator of caspases / direct IAP binding protein with low pI ) is second only to cytochrome c activator of caspases origin mitochondrial , whose function is to release caspases from the inhibitory effect of IAPs ( inhibitors of apoptotic proteases ) . Precursor Smac / DIABLO synthesized as 239- amino acid protein which, after linker BIR2 spatial structure , which in turn prevents binding of caspase 3 and 7 by the IAPs . Smac / DIABLO released from mitochondria is not only in the mitochondrial pathways of apoptosis but also the receptor . This is due to the fact that the apoptotic signal from death receptors via caspase -8 is too weak for the full activation of the caspase (3, 6 and 7) in cancer cells. Receptor signal must be amplified by the release of Smac / DIABLO from the mitochondria and the abolition of the inhibitory effect of IAPs on caspases . Interestingly, in this case usually does not occur until the release of mitochondrial cytochrome c , which may indicate a different molecular mechanism of release of the two proteins. Recent study using the homeostatic confocal microscopy , allowing a precise study of the kinetics of Smac / DIABLO in stimulated tumor cell apoptosis , showed the release of Smac / DIABLO -GFP from the mitochondria immediately after the application of cytotoxic drug . Blocking the activity of m- calpain ? activator Bax delayed the release of Smac / DIABLO -GFP from mitochondria and inhibits apoptosis. Our data using laser scanning cytometry , confocal microscopy and immunoelectron and literature data indicate the crucial role of Bax and possibly other proteins coformation of megachannels in the outer mitochondrial membrane in the regulation of Smac / DIABLO release from mitochondria

The Editorial Board
Andrzej Łukaszyk - przewodniczący, Zofia Bielańska-Osuchowska, Szczepan Biliński, Mieczysław Chorąży, Aleksander Koj, Włodzimierz Korochoda, Leszek Kuźnicki, Aleksandra Stojałowska, Lech Wojtczak

Editorial address:
Katedra i Zakład Histologii i Embriologii Uniwersytetu Medycznego w Poznaniu, ul. Święcickiego 6, 60-781 Poznań, tel. +48 61 8546453, fax. +48 61 8546440, email: mnowicki@ump.edu.pl

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