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HIF-1 and EGLN1 Under Hypobaric Hypoxia: Regulation of Master Regulator Paradigm

  • Aastha Mishra
  • M. A. Qadar Pasha
Chapter

Abstract

High-altitude (HA) populations living for several thousands of years at elevations up to 5,000 m present many adaptive phenotypic changes; conversely, the lowland populations respond differentially like acclimatizing to the environment or predisposing to HA disorders. Hypobaric hypoxia environment at HA results into reduced blood arterial O2 saturation in the body. It stimulates an array of physiological responses enabling the body to function optimally under this environment. Several of the physiological responses are regulated by hypoxia inducible factor-1 (HIF-1), a master transcription factor of O2-sensing pathway. It regulates transcription of those genes that are required for either increasing O2 availability or mediating responses to O2 deprivation such as reduction of ATP turnover rate of the body. Under normoxic state, however, HIF-I is repressed by HIF-prolyl hydroxylase 2 (EGLN1), which in actuality hydroxylates HIF1α to facilitate its degradation. Furthermore, the adaptive phenotypes are the result of natural selection of genetic traits that counteract the effects of environmentally induced changes. Identification of variants in these genes may help in elucidating molecular mechanisms by which these two molecules function under hypobaric hypoxia. These elucidated mechanisms can be translated for practical applications to enhance the health management at HA. It may also help in designing new therapeutic targets, thereby transforming the basic knowledge into practical applications.

Keywords

Carotid Body Hypobaric Hypoxia Acute Mountain Sickness Aryl Hydrocarbon Receptor Nuclear Translocator Chronic Mountain Sickness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The work presented here was supported by CSIR under the projects SIP0006, MLP1401, and EXP0016. We acknowledge the support and encouragement of the director, CSIR-IGIB, during the preparation of this manuscript.

Author Contributions

Aastha Mishra researched and wrote the manuscript. Qadar Pasha conceptualized, researched, wrote, and edited the manuscript.

Conflicts of Interest

We declare that we have no conflicts of interest.

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Copyright information

© Springer India 2014

Authors and Affiliations

  1. 1.Functional Genomics UnitCSIR-Institute of Genomics and Integrative BiologyDelhiIndia

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