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Effect of Antioxidant Enzymes on Hypoxia-Induced HIF-$1{\alpha}$ Accumulation and Erythropoietin Activity  

Cho, Eun-Jin (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Cho, Ki-Woon (Department of Oral Biochemistry, College of Dentistry, Chosun University)
Chung, Kyoung-Jin (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Yang, Hee-Young (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Park, Hyang-Rim (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Park, Byung-Ju (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Lee, Tae-Hoon (School of Dentistry, Dental Science Research Institute, The 2nd Stage of Brain Korea 21 for the Dental School, Chosun University)
Publication Information
International Journal of Oral Biology / v.34, no.4, 2009 , pp. 205-213 More about this Journal
Abstract
The mechanisms underlying the actions of the antioxidants upon reactive oxygen species (ROS) generation by NADPH oxidase complex have remained uncertain. In this study, we investigated NADPH oxidase activity and the role of antioxidant enzymes upon the generation of ROS during hypoxic stress. ROS generation was found to increase in the mouse kidney under hypoxic stress in a time-dependent manner. Moreover, we found in MCT cells that hypoxia-induced hydrogen peroxide production was decreased by NAC pretreatment. We further analyzed HIF-$1{\alpha}$, PHD2 and VHL expression in the NAC-pretreated MCT cells and assessed the response of antioxidant enzymes at the transcriptional and translational levels. SOD3 and Prdx2 were significantly increased during hypoxia in the mouse kidney. We also confirmed in hypoxic $Prdx2^{-/-}$ and SOD3 transgenic mice that erythropoietin (EPO) is transcriptionally regulated by HIF-$1{\alpha}$. In addition, although EPO protein was found to be expressed in a HIF-$1{\alpha}$ independent manner in three mouse lines, its activity differed markedly between normal and $Prdx2^{-/-}$/SOD3 transgenic mice during hypoxic stress. In conclusion, our current results indicate that NADPH oxidase-mediated ROS generation is associated with hypoxic stress in the mouse kidney and that SOD3 and Prdx2 cooperate to regulate cellular redox reactions during hypoxia.
Keywords
hypoxia; reactive oxygen species; NADPH oxidase; peroxiredoxin 2; superoxide dismutase 3; erythropoietin;
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