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J. Biol. Chem., Vol. 278, Issue 10, 8516-8525, March 7, 2003
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From the Inhibition of mitochondrial respiratory chain
complex I by rotenone had been found to induce cell death in a variety
of cells. However, the mechanism is still elusive. Because reactive
oxygen species (ROS) play an important role in apoptosis and inhibition of mitochondrial respiratory chain complex I by rotenone was
thought to be able to elevate mitochondrial ROS production, we
investigated the relationship between rotenone-induced apoptosis and
mitochondrial reactive oxygen species. Rotenone was able to induce
mitochondrial complex I substrate-supported mitochondrial ROS
production both in isolated mitochondria from HL-60 cells as well as in
cultured cells. Rotenone-induced apoptosis was confirmed by DNA
fragmentation, cytochrome c release, and caspase 3 activity. A quantitative correlation between rotenone-induced apoptosis
and rotenone-induced mitochondrial ROS production was identified.
Rotenone-induced apoptosis was inhibited by treatment with antioxidants
(glutathione, N-acetylcysteine, and vitamin C). The role of
rotenone-induced mitochondrial ROS in apoptosis was also confirmed by
the finding that HT1080 cells overexpressing magnesium superoxide
dismutase were more resistant to rotenone-induced apoptosis than
control cells. These results suggest that rotenone is able to
induce apoptosis via enhancing the amount of mitochondrial reactive
oxygen species production.
Mitochondrial Complex I Inhibitor Rotenone Induces
Apoptosis through Enhancing Mitochondrial Reactive Oxygen Species
Production*
,,,,,¶
Purdue University Cytometry Laboratories,
Department of Basic Medical Sciences, Purdue University, West
Lafayette, Indiana 47907 and the § Center for Immunology & Microbial Disease, MC-151, Albany Medical College, Albany, New York
12208
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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