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Expression-Regulation of Hif-Induced Gene and Oxidative Stress Gene in Acute Hypobaric Hypoxia

Mirza Asad Beg, Imteyaz Qamar


Hypoxia is condition in which body or some region of the body is deprived of adequate supply of oxygen. Adaptation to hypoxia is required by animals and human in several physiological and pathological situations. Hypobaric hypoxia is a pathophysiological condition which triggers redox status disturbances of cell organization leading, via an oxidative stress, to proteins, lipids and DNA damage. Identifying the molecular variables playing key roles in this process would be of paramount importance to shed light on the mechanisms known to counteract the negative effects of oxygen lack. To obtain a molecular signature, I will check the expression of the regulation of HIF induced gene and oxidative stress gene in hypobaric hypoxia, because HIF1 alpha is present in rat kept under normoxic conditions and is further increased in response to hypobaric hypoxia. Hypoxia response elements containing HIF-1 binding sites were identified in genes encoding transferrin, inducible nitric oxide synthase (iNOS), and several glycolytic enzymes, all playing important roles in systemic tissues, or intercellular O2 homeostasis allowing for increased anaerobic ATP synthesis. Adaptation to hypoxia is regulated by hypoxia inducible factor 1 (HIF1). Although HIF1 is regulated mainly by oxygen regulated tension through the oxygen-dependent degradation of its alpha-subunit. By comparing the expression of genes in hypoxic rats, the rats which are treated by a drug and with those of a normal control group, several genes with significant expressions were found. The up-regulated genes were identified as NOS2, HSP70, EpoVar-X1, SLC2A1, HIF1. These results were further validated by PCR analysis.

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