当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Enhanced metallothionein gene expression induced by mitochondrial oxidative stress is reduced in phospholipid hydroperoxide glutathione peroxidase-overexpressed cells.

Enhanced metallothionein gene expression induced by mitochondrial oxidative stress is reduced in phospholipid hydroperoxide glutathione peroxidase-overexpressed cells.

Abstract：

:Mitochondria are major compartments in cells responsible for generating reactive oxygen species, which can cause the development of diabetes, Parkinson's disease and premature aging. Antioxidant systems in mitochondria are important for the prevention of diseases and reduction in the speed of aging. We investigated whether the reactive oxygen species generated in mitochondria induced the expression of metallothionein as an antioxidant. We compared the expression level of metallothionein mRNA in mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx)-overexpressed (PHGPx-ov) cells with that in control cells. These cells were treated with respiratory inhibitors, including rotenone and 2, 4-dinitrophenol; under these conditions, the PHGPx-ov cells were more resistant to cell death than the control cells. In addition, the intracellular reactive oxygen species level that was induced by these inhibitors was lower in PHGPx-ov cells than in control cells. This indicates that PHGPx degrades the membrane phospholipid hydroperoxide that is formed via the reactive oxygen species generated in mitochondria. The enhanced expression of metallothionein-I and metallothionein-II mRNA in rotenone-treated control cells was significantly decreased in rotenone-treated PHGPx-ov cells, suggesting that the hydrogen peroxide that is formed by superoxide anions generated in mitochondria diffuse into the cytosol and induce metallothionein mRNA expression. Conversely, the expression of manganese-superoxide dismutase (Mn-SOD) mRNA, which is localized in mitochondria, was not correlated with the intracellular reactive oxygen species level that was induced by rotenone treatment. These results suggest that metallothionein expression is sensitively and strictly regulated by the oxidative state that is induced by mitochondrial respiration.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Kadota Y,Suzuki S,Ideta S,Fukinbara Y,Kawakami T,Imai H,Nakagawa Y,Sato M

doi

10.1016/j.ejphar.2009.09.060

subject

Has Abstract

pub_date

2010-01-25 00:00:00

pages

166-70

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(09)00844-9

journal_volume

626

pub_type

杂志文章

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