Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress.
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.
Surh
Young-Joon
YJ
Seoul National University, Korea. surh@plaza.snu.ac.kr
Kundu
Joydeb Kumar
JK
Li
Mei-Hua
MH
Na
Hye-Kyung
HK
Cha
Young-Nam
YN
D000222:Adaptation, Physiological; D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology; D016923:Cell Death; D002470:Cell Survival; D019610:Cytoprotection; D005721:Glutamate-Cysteine Ligase / Q000502:physiology; D005978:Glutathione / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D010766:Phosphorylation; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D013312:Stress, Physiological; D015854:Up-Regulation
D051267:NF-E2-Related Factor 2; D026361:Reactive Nitrogen Species; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione