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Ruthenium red, inhibitor of mitochondrial Ca2+ uniporter, inhibits curcumin-induced apoptosis via the prevention of intracellular Ca2+ depletion and cytochrome c release

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Author(s)
배재훈박종욱권택규
Alternative Author(s)
Bae, Jae HoonPark, Jong WookKwon, Taeg Kyu
Publication Year
2003
Abstract
Curcumin, a natural, biologically active compound extracted from rhizomes of Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor, and anti-oxidative properties. The mechanism by which curcumin initiates apoptosis remains poorly understood. In the present report we investigated the effect of curcumin on the activation of the apoptotic pathway in human leukemia U937 cells. Curcumin induces apoptosis in U937 cells via a mechanism that appears to involve down-regulation of the anti-apoptotic Bcl-xL, and IAP proteins, release of cytochrome c, and activation of caspase 3. Ruthenium red, an inhibitor of mitochondrial uniporter, specifically inhibits curcumin-induced apoptosis in U937 cells. Cotreatment with ruthenium red markedly prevented the activation of caspase 3, cytochrome c release, and cell death, suggesting a role for intracellular Ca2+ in this process. Curcumin induced a marked depletion of [Ca2+]i in Caki cells bathed with both Ca2+-containing and -free solutions. Thapsigargin (TG), cyclopiazonic acid (CPA), and dantolene (DAN) had no effect. Ruthenium red, an inhibitor of mitochondrial uniporter, only attenuated the curcumin-induced [Ca2+]i depletion in a dose-dependent manner. These data indicate that curcumin acts as a stimulator of intracellular Ca2+ uptake into mitochondria via uniporter pathway and may involve in the execution of apoptosis.

Keywords
Curcumin;
Apoptosis;
Ruthenium red;
Ca2+ uptake;
Mitochondrial uniporter
Department
Dept. of Physiology (생리학)
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.303(4) : 1073-1079, 2003
Type
Article
ISSN
0006-291X
DOI
10.1016/S0006-291X(03)00479-0
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35152
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