Depletion of Branched-chain Aminotransferase 2 (BCAT2) Enzyme Impairs Myoblast Survival and Myotube Formation

Overview

Journal Physiol Rep

Specialty Physiology

Date 2019 Dec 14

PMID 31833233

Citations 7

Authors

Zameer N Dhanani

Gagandeep Mann

Olasunkanmi A J Adegoke

Affiliations

Soon will be listed here.

Abstract

Much is known about the positive effects of branched-chain amino acids (BCAA) in regulating muscle protein metabolism. Comparatively much less is known about the effects of these amino acids and their metabolites in regulating myotube formation. Using cultured myoblasts, we showed that although leucine is required for myotube formation, this requirement is easily met by α-ketoisocaproic acid, the ketoacid of leucine. We then demonstrated increases in the expression of the first two enzymes in the catabolism of the three BCAA, branched-chain amino transferase (BCAT2) and branched-chain α-ketoacid dehydrogenase (BCKD), with ~3× increase in BCKD protein expression (p < .05) during differentiation. Furthermore, depletion of BCAT2 abolished myoblast differentiation, as indicated by reduction in the levels of myosin heavy chain-1, troponin and myogenin. Supplementation of incubation medium with branched-chain α-ketoacids or related metabolites derivable from BCAT2 functions did not rescue the defects. However, co-depletion of BCKD kinase partially rescued the defects. Collectively, our data indicate a requirement for BCAA catabolism during myotube formation and that this requirement for BCAT2 likely goes beyond the need for this enzyme to generate the α-ketoacids of the BCAA.

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