Dataset Information

Skeletal muscle PGC-1? controls whole-body lactate homeostasis through estrogen-related receptor ?-dependent activation of LDH B and repression of LDH A.

ABSTRACT: The peroxisome proliferator-activated receptor-? coactivator 1? (PGC-1?) controls metabolic adaptations. We now show that PGC-1? in skeletal muscle drives the expression of lactate dehydrogenase (LDH) B in an estrogen-related receptor-?-dependent manner. Concomitantly, PGC-1? reduces the expression of LDH A and one of its regulators, the transcription factor myelocytomatosis oncogene. PGC-1? thereby coordinately alters the composition of the LDH complex and prevents the increase in blood lactate during exercise. Our results show how PGC-1? actively coordinates lactate homeostasis and provide a unique molecular explanation for PGC-1?-mediated muscle adaptations to training that ultimately enhance exercise performance and improve metabolic health.

SUBMITTER: Summermatter S

PROVIDER: S-EPMC3666691 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A.

Summermatter Serge S Santos Gesa G Pérez-Schindler Joaquín J Handschin Christoph C

Proceedings of the National Academy of Sciences of the United States of America 20130506 21

The peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) controls metabolic adaptations. We now show that PGC-1α in skeletal muscle drives the expression of lactate dehydrogenase (LDH) B in an estrogen-related receptor-α-dependent manner. Concomitantly, PGC-1α reduces the expression of LDH A and one of its regulators, the transcription factor myelocytomatosis oncogene. PGC-1α thereby coordinately alters the composition of the LDH complex and prevents the increase in blood lactate ...[more]

PMID: 23650363

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Project description: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.

Dataset Information

Skeletal muscle PGC-1? controls whole-body lactate homeostasis through estrogen-related receptor ?-dependent activation of LDH B and repression of LDH A.

Publications

Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A.

Similar Datasets

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