Oxidative Stress-Induced Necrotic Cell Death via Mitochondira-Dependent Burst of Reactive Oxygen Species

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Oxidative stress is deeply involved in various brain diseases, including neurodegenerative diseases, stroke, and ischemia/reperfusion injury. Mitochondria are thought to be the target and source of oxidative stress. We investigated the role of mitochondria in oxidative stress-induced necrotic neuronal cell death in a neuroblastoma cell line and a mouse model of middle cerebral artery occlusion. The exogenous administration of hydrogen peroxide was used to study the role of oxidative stress on neuronal cell survival and mitochondrial function in vitro. Hydrogen peroxide induced nonapoptotic neuronal cell death in a c-Jun N-terminal kinase- and poly(ADP-ribosyl) polymerase-dependent manner. Unexpectedly, hydrogen peroxide treatment induced transient hyperpolarization of the mitochondrial membrane potential and a subsequent delayed burst of endogenous reactive oxygen species (ROS). The inhibition of mitochondrial hyperpolarization by diphenylene iodonium or rotenone, potent inhibitors of mitochondrial respiratory chain complex I, resulted in reduced ROS production and subsequent neuronal cell death in vitro and in vivo. The inhibition of mitochondrial hyperpolarization can protect neuronal cells from oxidative stress-induced necrotic cell death, suggesting a novel method of therapeutic intervention in oxidative stress-induced neurological disease.
Publisher
BENTHAM SCIENCE PUBL LTD
Issue Date
2009-11
Language
English
Article Type
Article
Keywords

N-TERMINAL KINASE; PERMEABILITY TRANSITION; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; HYDROGEN-PEROXIDE; COMPLEX-I; APOPTOSIS; SUPEROXIDE; BRAIN; RAT

Citation

CURRENT NEUROVASCULAR RESEARCH, v.6, pp.213 - 222

ISSN
1567-2026
URI
http://hdl.handle.net/10203/97126
Appears in Collection
BiS-Journal Papers(저널논문)
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