Apoptosis and the conformational change of Bax induced by proteasomal inhibition of PC12 cells are inhibited by bcl-xL and bcl-2

Apoptosis : an International Journal on Programmed Cell Death
Isabelle Lang-RollinL Stefanis

Abstract

The function of the proteasome has been linked to various pathologies, including cancer and neurodegeneration. Proteasomal inhibition can lead to death in a variety of cell types, however the manner in which this occurs is unclear, and may depend on the particular cell type. In this work we have extended previous findings pertaining to the effects of pharmacological proteasomal inhibitors on PC12 cells, by examining in more detail the induced death pathway. We find that cell death is apoptotic by ultrastructural criteria. Caspase 9 and 3 are processed, cytochrome c is released from the mitochondria and a dominant negative form of caspase 9 prevents death. Furthermore, Bax undergoes a conformational change and is translocated to the mitochondria in a caspase-independent fashion. Total cell levels of Bax however do not change, whereas levels of the BH3-only protein Bim increase with proteasomal inhibition. Transient overexpression of bcl-xL or, to a lesser extent, of bcl-2, significantly decreased apoptotic death and prevented Bax conformational change. We conclude that death elicited by proteasomal inhibition of PC12 cells follows a classical "intrinsic" pathway. Significantly, antiapoptotic bcl-2 family members prevent apoptosi...Continue Reading

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Citations

Apr 7, 2007·Apoptosis : an International Journal on Programmed Cell Death·Luena PapaPatricia Rockwell
May 6, 2008·Apoptosis : an International Journal on Programmed Cell Death·Lakshmishri LahiryTanya Das
Oct 26, 2012·The Journal of Biological Chemistry·Yoshitaka TashiroRyosuke Takahashi
Dec 3, 2005·The Cerebellum·Emmanuelle Bitoun, Kay Elizabeth Davies
Mar 19, 2014·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Jia-Ming Mei, Chao-Shi Niu
Apr 18, 2013·The International Journal of Neuroscience·Jun Ping CaoDian Shuai Gao
Sep 30, 2009·British Journal of Pharmacology·Sergio Perez-AlvarezMaría F Galindo
Jun 14, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qunxing DingJeffrey N Keller
Jan 1, 2014·International Journal of Molecular Medicine·Zuanfang LiLidian Chen
Oct 5, 2006·Cancer Research·Jian-Zhong QinBrian J Nickoloff

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