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KMID : 0043320090320081163
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Archives of Pharmacal Research
2009 Volume.32 No. 8 p.1163 ~ p.1176
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Role of Nrf2-Mediated Heme Oxygenase-1 Upregulation in Adaptive Survival Response to Nitrosative Stress
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Cha Young-Nam
Surh Young-Joon
Li Mei-Hua
Kundu Joydeb Kumar
Na Hye-Kyung
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Abstract
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Nitrosative stress caused by reactive nitrogen species such as nitric oxide and peroxynitrite overproduced during inflammation leads to cell death and has been implicated in the pathogenesis of many human ailments. However, relatively mild nitrosative stress may fortify cellular defense capacities, rendering cells tolerant or adaptive to ongoing and subsequent cytotoxic challenges, a phenomenon known as ‘preconditioning’ or ‘hormesis’. One of the key components of cellular stress response is heme oxygenase-1 (HO-1), the rate limiting enzyme in the process of degrading potentially toxic free heme into biliverdin, free iron and carbon monoxide. HO-1 is upregulated by a wide array of stimuli and has antioxidant, anti-inflammatory and other cytoprotective functions. This review is intended to provide readers with a welldocumented account of the research done in the area of cellular adaptive survival response against nitrosative stress with special focus on the role of HO-1 upregulation, especially through activation of the transcription factor, Nrf2.
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KEYWORD
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Heme oxygenase-1, Nrf2, Nitrosative stress, Nitric oxide, Peroxynitrite
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