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Oxidative protein modification alters proteostasis under acute hypobaric hypoxia in skeletal muscles: a comprehensive in vivo study

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Cell Stress and Chaperones Aims and scope

Abstract

While numerous maladies are associated with hypobaric hypoxia, muscle protein loss is an important under studied topic. Hence, the present study was designed to investigate the mechanism of muscle protein loss at HH. SD rats were divided into normoxic rats, while remaining rats were exposed to simulated hypoxia equivalent to 282-torr pressure (equal to an altitude of 7620 m, 8% oxygen), at 25 °C for 6, 12, and 24 h. Post-exposure rats were sacrificed and analysis was performed. Ergo, muscle loss-related changes were observed at 12 and 24 h post-HH exposure. An increased reactive oxygen species production and decreased thiol content was observed in HH-exposed rats. This disturbance caused substantial protein oxidative modification in the form of protein carbonyl content and advanced oxidation protein products. The analysis showed increase levels of bityrosine, oxidized tryptophan, lysine conjugate, lysine conjugate with MDA, protein hydroperoxide, and protein-MDA product. These changes were also in agreement with increase in lipid hydroperoxides and MDA content. HSP-70 and HSP-60 were upregulated significantly, and this finding is corroborated with increase in ER stress biomarker, GRP-78. Overloading of cells with misfolded proteins further activated degradative machinery. Consequently, pro-apoptotic signaling cascade, caspase-3, and C/EBP homologous protein were also activated in 24-h HH exposure. Release of tryptophan and tyrosine was also increased with 24-h HH exposure, indicated protein degradation. Elevation in resting intracellular calcium ion, [Ca2+]i, was also observed at 12- and 24-h HH exposure. The present study provides a detailed mechanistic representation of muscle protein loss during HH exposure.

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Abbreviations

HH:

Hypobaric hypoxia

GRP:

Glucose regulating protein

HSP:

Heat shock protein

AOPP:

Advanced oxidation protein product

MDA:

Malondialdehyde

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Acknowledgements

The authors are thankful to Dr. (Mrs.) Shashi Bala Singh, Director, DIPAS, for her constant support and encouragement. One of the authors, Ms. Akanksha Agrawal, is thankful for obtaining Senior Research Fellowship from DRDO.

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  1. Cellular Biochemistry Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi -54, India

    Akanksha Agrawal, Richa Rathor & Geetha Suryakumar

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  1. Akanksha Agrawal
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  2. Richa Rathor
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Correspondence to Richa Rathor.

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Agrawal, A., Rathor, R. & Suryakumar, G. Oxidative protein modification alters proteostasis under acute hypobaric hypoxia in skeletal muscles: a comprehensive in vivo study. Cell Stress and Chaperones 22, 429–443 (2017). https://doi.org/10.1007/s12192-017-0795-8

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