Neuroglobin Regulates Hypoxic Response of Neuronal Cells through Hif-1α- and Nrf2-mediated Mechanism
Open Access
- 4 April 2012
- journal article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 32 (6), 1046-1060
- https://doi.org/10.1038/jcbfm.2012.21
Abstract
Oxygen sensing in hypoxic neurons has been classically attributed to cytochrome c oxidase and prolyl-4-hydroxylases and involves stabilization of transcription factors, hypoxia-inducible factor-1α (Hif-1α) and nuclear factor erythroid 2-related factor 2 (Nrf2) that mediate survival responses. On the contrary, release of cytochrome c into the cytosol during hypoxic stress triggers apoptosis in neuronal cells. We, here advocate that the redox state of neuroglobin (Ngb) could regulate both Hif-1α and Nrf2 stabilization and cytochrome c release during hypoxia. The hippocampal regions showing higher expression of Ngb were less susceptible to global hypoxia-mediated neurodegeneration. During normoxia, Ngb maintained cytochrome c in the reduced state and prevented its release from mitochondria by using cellular antioxidants. Greater turnover of oxidized cytochrome c and increased utilization of cellular antioxidants during acute hypoxia altered cellular redox status and stabilized Hif-1α and Nrf2 through Ngb-med...Keywords
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