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A Pathway of Neuronal Apoptosis Induced by Hypoxia/Reoxygenation
Author(s) -
Tamatani Michio,
Mitsuda Noriaki,
Matsuzaki Hideo,
Okado Haruo,
Miyake Shinichi,
Vitek Michael P,
Yamaguchi Atsushi,
Tohyama Masaya
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750683.x
Subject(s) - apoptosis , cytochrome c , programmed cell death , signal transduction , hypoxia (environmental) , microbiology and biotechnology , mitochondrion , caspase , biology , chemistry , biochemistry , oxygen , organic chemistry
As a model of the reperfusion injury found in stroke, we have exposed neurons to hypoxia followed by reoxygenation. Neurons treated with hypoxia/reoxygenation (H/R) respond by activating nuclear factor‐κB (NFκB), releasing cytochrome c from their mitochondria, and ultimately dying. Further supporting an apoptotic mechanism, expression of the antiapoptotic Bcl‐2 and Bcl‐x proteins was increased following H/R. In this model, adenoviral‐mediated transduction of lκB expression inhibited NFκB activation and significantly accelerated cytochrome c release and caspase‐dependent neuronal death. At the same time, expression of mutated lκB prevented the increased expression of endogenous Bcl‐2 and Bcl‐x. In the presence of mutated lκB, singular overexpression of only Bcl‐2 by adenoviral‐mediated transduction significantly inhibited cytochrome c release, caspase‐3‐like activation, and cell death in response to H/R. These findings suggest a pathway where NFκB activation induces overexpression of Bcl‐2 and Bcl‐x, which function to prevent apoptotic cell death following H/R treatments.