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Int. J. Environ. Res. Public Health 2015, 12(8), 9218-9236; doi:10.3390/ijerph120809218

Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances Apika’s Sprint-Running Capacity in Hypoxic Environment

Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China
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Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 5 July 2015 / Revised: 22 July 2015 / Accepted: 29 July 2015 / Published: 7 August 2015
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Abstract

LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai-Tibet plateau can adapt to the hypoxia environment. View Full-Text
Keywords: testis-specific lactate dehydrogenase C (LDH-C4); hypoxia; Qinghai-Tibet Plateau; plateau pika (Ochotona curzoniae); skeletal muscle testis-specific lactate dehydrogenase C (LDH-C4); hypoxia; Qinghai-Tibet Plateau; plateau pika (Ochotona curzoniae); skeletal muscle
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, Y.; Wei, L.; Wei, D.; Li, X.; Xu, L.; Wei, L. Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances Apika’s Sprint-Running Capacity in Hypoxic Environment. Int. J. Environ. Res. Public Health 2015, 12, 9218-9236.

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