Fluoxetine (Prozac) interaction with the mitochondrial voltage-dependent anion channel and protection against apoptotic cell death

被引：83

作者：

Nahon, E ^{[1
]}

Israelson, A ^{[1
]}

Abu-Hamad, S ^{[1
]}

Shoshan-Barmatz, V ^{[1
]}

机构：

[1] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel

来源：

FEBS LETTERS | 2005年 / 579卷 / 22期

基金：

以色列科学基金会;

关键词：

voltage-dependent anion channel; fluoxetine; Prozac; permeability transition pore; apoptosis; cytochrome c;

D O I：

10.1016/j.febslet.2005.08.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Fluoxetine (Prozac) is a potent antidepressant compound inhibiting serotonin reuptake, but also Na+, K+ and Ca2+ channels and reported to both trigger and prevent apoptosis. Recently, fluoxetine was found to increase the voltage sensitivity of the mitochondrial voltage-dependent anion channel (VDAC). VDAC which functions in transporting metabolites across the mitochondria also plays a crucial role in apoptosis. Here, we demonstrate that fluoxetine interacted with VDAC and decreased its conductance. Fluoxetine inhibited the opening of the mitochondrial permeability transition pore, the release of cytochrome c, and protected against staurosporine-induced apoptotic cell death. These findings may explain some of the reported fluoxetine side effects. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：5105 / 5110

页数：6

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