Superoxide anion regulates the mitochondrial free Ca2+ through uncoupling proteins.
 

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04-14-09 08:19 AM
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Superoxide anion regulates the mitochondrial free Ca2+ through uncoupling proteins.
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Superoxide anion regulates the mitochondrial free Ca2+ through uncoupling proteins.

Antioxid Redox Signal. 2009 Apr 10;

Authors: Wu Z, Zhang J, Zhao B

Mitochondrial dysfunction, which is closely related to intracellular calcium overload and excessive free radicals, is an important cause of Alzheimer's disease (AD). However, molecular mechanisms of the mitochondrial Ca2+ disregulation induced by oxidative stress in AD are still obscure. In an effort to gain a further understanding for this question, we investigated the effects of superoxide anion, a primary free radical, on the expression of uncoupling proteins (UCPs) and the mitochondrial free Ca2+ levels in the neuroblastoma SH-SY5Y cell line (neo) and stable expressed wild-type human APP(APP) and APP-Swedish mutation (APPsw) SH-SY5Y cells. It was found that UCP2 and UCP4 protein levels were up-regulated in neo but down regulated in APP and APPsw cells by superoxide anion. Our results show superoxide anion can regulate protein levels of UCP2 and UCP4 in SH-SY5Y cells and the mitochondrial free Ca2+ shifted their levels tightly coupled with the protein levels of UCPs. When UCP2 and UCP4 were knocked down by siRNA, the result was reversed. These data suggest that superoxide anion can regulate the mitochondrial free Ca2+ by regulating the expression of UCPs. These observations also indicate UCPs can be potential targets in pathotherapy prevention of AD.

PMID: 19361273 [PubMed - as supplied by publisher]