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Low- and high-dose hydrogen peroxide regulation of transcription factor NF-E2-related factor 2

Chinese Medical Journal 2010年第8期123卷 1063-1069页

作者： NING Jiao-lin MO Li-wen LAI Xi-nan Department of Anesthesia Southwest Hospital Third Military Medical University Chongqing 400038 China Department of Nephrology People's Liberation Army Chengdu Military Area Command General Hospital Chengdu Sichuan 610083 China State Key Laboratory of Trauma Burns and Combined injury Institute of Surgery Research Department of Traumatic Surgery Daping Hospital Third Melitary Medical University Chongqing 400042 China

Background Reactive oxygen species （ROS） may play both physiological and pathophysiological roles. Transcription factor NF-E2-related factor 2 （Nrf2） regulates antioxidant response element （ARE）-mediated genes expression and coordinates induction of chemoprotective proteins in response to physical and chemical stresses. The exact role of Nrf2 in cellular responses to different levels of oxidative stresses remains unknown. Methods Rat pulmonary microvascular endothelial cells were cultured and treated with 0 mmol/L, 0.125 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L hydrogen peroxide solution for 2 hours. Nrf2 gene expression was assayed by reverse transcription-PCR, Nrf2-ARE binding activity was assayed with electrophoretic mobility shift assay （EMSA）, and localization of Nrf2 was detected with immunohistochemistry. Results Low and moderate （0.125 mmol/L, 0.25 mmol/L and 0.5 mmol/L） doses hydrogen peroxide exposure of rat pulmonary microvascular endothelial cells led to the nuclear accumulation of Nrf2, increased activity of transcription regulation and up-regulation of ARE-medicated gene expression. In contrast, high doses of hydrogen peroxide （1 mmol/L 2 mmol/L） exposure of the cells led to the nuclear exclusion of Nrf2, decreased activity transcription regulation and down-regulation of ARE-mediated gene expression. Conclusion Low and moderate doses of hydrogen peroxide play protective roles by increasing transcription activity of Nrf2, whereas high- dose hydrogen peroxide plays a deleterious role by decreasing transcription activity of Nrf2.

关键词： pulmonary micro-vascular endothelial cells antioxidant responsive element, hydrogen peroxide NF-E2-related factor 2

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