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KMID : 0811719970010020209
Korean Journal of Physiology & Pharmacology
1997 Volume.1 No. 2 p.209 ~ p.219
Reduction of TNF ¥á-induced Oxidative DNA Damage Product, 8-Hydroxy-2'-Deoxyguanosine, in L929 Cells Stably Transfected with Small Heat Shock Protein
Young-Mee Park
Eun-Mi Choi
Abstract
Previous studies have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of TNF¥á. Protective effect of small heat shock proteins (small HSP) against diverse oxidative stress conditions has been suggeted. Although overexpression of small hsp was shown to provide an enhanced survival of TNF¥á-sensitive cells when challenged with TNF¥á, neither the nature of TNF¥á-induced cytotoxicity nor the protective mechanism of small HSP has not been completely understood. In this study, we have attempted to determine whether TNF¥á induces oxidative DNA damage in TNF¥á-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2'-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a TNF¥á dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on TNF¥á-induced oxidative DNA damage. To accomplish this goal, we have stably transfected L929 cells with mouse small hsp cDNA (hsp25) since these cells are devoid of endogenous small hsps. We found that TNF¥á-induced 8 ohdG was decreased in cells overexpressing exogenous small hsp. We also found that the cell killing activity of TNF¥á was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that cytotoxic mechanism of TNF¥á involves oxidative damage of DNA and that overexpression of the small hsp reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is one of the most important protective mechanisms of small HSP against TNF¥á.
KEYWORD
TNF ¥á, HSP, Oxidative DNA damage, 8 ohdG,
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