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

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Translational Research in Environmental and Occupational Stress

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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.

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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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Authors and Affiliations

  1. Functional Genomics Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, India

    Aastha Mishra & M. A. Qadar Pasha

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  1. Aastha Mishra
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  2. M. A. Qadar Pasha
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Correspondence to M. A. Qadar Pasha .

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  1. Defence Institute of Physiology and Allied Sciences (DIPAS), New Delhi, Delhi, India

    Shashi Bala Singh

  2. Department of Medicine and Director for Systems, The University of Chicago, Chicago, USA

    Nanduri R. Prabhakar

  3. Department of Anaesthesiology, School of Medicine, State University of New York, Stony Brook, New York, USA

    Srinivas N Pentyala

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Mishra, A., Pasha, M.A.Q. (2014). HIF-1 and EGLN1 Under Hypobaric Hypoxia: Regulation of Master Regulator Paradigm. In: Singh, S., Prabhakar, N., Pentyala, S. (eds) Translational Research in Environmental and Occupational Stress. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1928-6_8

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