Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika's Sprint-Running Capacity in Hypoxic Environment.
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.
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. yangwangmd@163.com.
Yang
Y
Wang
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. weilian5318@163.com.
Lian
L
Wei
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. weidengbang@163.com.
Dengbang
D
Wei
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. lixiao2234566@163.com.
Xiao
X
Li
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. xu020916@163.com.
Lina
L
Xu
Research Center for High Altitude Medicine, Qinghai University, Xining 810016, China. weilian5318@163.com.
Linna
L
Wei
D000064:Acclimatization; D000818:Animals; D007273:Injections, Intramuscular; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D007793:Lagomorpha / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011897:Random Allocation; D012420:Running; D013737:Testis / Q000378:metabolism; D018609:Tibet
D007527:Isoenzymes; C109929:N-isopropyloxamate; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C409667:lactate dehydrogenase 1; C409673:lactate dehydrogenase C4; D010072:Oxamic Acid; D010100:Oxygen
Qinghai-Tibet Plateau; hypoxia; plateau pika (Ochotona curzoniae); skeletal muscle; testis-specific lactate dehydrogenase C (LDH-C4)