Over-expression of Senescence Marker Protein-30 Decreases Reactive Oxygen Species in Human Hepatic Carcinoma Hep G2 Cells
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概要
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Senescence Marker Protein-30 (SMP30) is an androgen-independent factor that decreases with aging. We recently characterized SMP30 as a gluconolactonase (GNL) involved in the biosynthetic pathway of vitamin C and established that SMP30 knockout mice could not synthesize vitamin C in vivo. Although mice normally synthesize vitamin C, humans are prevented from doing so by mutations that have altered the gluconolactone oxidase gene during evolution. Even the SMP30/GNL present abundantly in the human liver does not synthesize vitamin C in vivo. To clarify the functions of this SMP30/GNL, we transfected the human SMP30/GNL gene into the human liver carcinoma cell line, Hep G2. The resulting Hep G2/SMP30 cells expressed approximately 10.9-fold more SMP30/GNL than Hep G2/pcDNA3 mock-transfected control cells. Examination of SMP30/GNLs impact on the state of oxidative stress in these cells revealed that formation of the reactive oxygen species (ROS) of mitochondrial and post-mitochondrial fractions from Hep G2/SMP30 cells decreased by a significant 24.0% and 18.1%, respectively, compared to those from Hep G2/pcDNA3 cells. Lipid peroxidation levels in Hep G2/SMP30 cells similarly decreased. Moreover, levels of the antioxidants superoxide dismutase (SOD) and glutathione (GSH) in Hep G2/SMP30 cells were a significant 42.6% and 62.4% lower than those in Hep G2/pcDNA3 cells, respectively. Thus, over-expression of SMP30/GNL in Hep G2 cells contributed to a decrease of ROS formation accompanied by decreases of lipid peroxidation, SOD activity and GSH levels.
- 公益社団法人 日本薬学会の論文
著者
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MARUYAMA Naoki
Aging Regulation, Tokyo Metropolitan Institute of Gerontology
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Maruyama Naoki
Tokyo Metropolitan Institute Of Gerontology Keio University
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HANDA Setsuko
Aging Regulation, Tokyo Metropolitan Institute of Gerontology
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Maruyama N
Energy System Design Laboratory Department Of Mechanical Engineering Mie University
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Maruyama N
Tokyo Noko Univ. Tokyo Jpn
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Ishigami Akihito
Dep. Of Biochemistry Fac. Of Pharmaceutical Sciences Toho Univ.
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Ishigami Akihito
Aging Regulation Tokyo Metropolitan Institute Of Gerontology
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Maruyama Nobuyuki
Tokyo Metropolitan Institute Of Gerontology
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Maruyama Naoki
Aging Regulation Tokyo Metropolitan Institute Of Gerontology
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Handa Setsuko
Tokyo Metropolitan Inst. Gerontology Tokyo Jpn
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Ishigami Akihito
Aging Regulation, Tokyo Metropolitan Institute of Gerontology
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