Global deletion of BCATm increases expression of skeletal muscle genes associated with protein turnover

Physiological Genomics
Christopher J LynchYuka Imamura Kawasawa

Abstract

Consumption of a protein-containing meal by a fasted animal promotes protein accretion in skeletal muscle, in part through leucine stimulation of protein synthesis and indirectly through repression of protein degradation mediated by its metabolite, α-ketoisocaproate. Mice lacking the mitochondrial branched-chain aminotransferase (BCATm/Bcat2), which interconverts leucine and α-ketoisocaproate, exhibit elevated protein turnover. Here, the transcriptomes of gastrocnemius muscle from BCATm knockout (KO) and wild-type mice were compared by next-generation RNA sequencing (RNA-Seq) to identify potential adaptations associated with their persistently altered nutrient signaling. Statistically significant changes in the abundance of 1,486/∼39,010 genes were identified. Bioinformatics analysis of the RNA-Seq data indicated that pathways involved in protein synthesis [eukaryotic initiation factor (eIF)-2, mammalian target of rapamycin, eIF4, and p70S6K pathways including 40S and 60S ribosomal proteins], protein breakdown (e.g., ubiquitin mediated), and muscle degeneration (apoptosis, atrophy, myopathy, and cell death) were upregulated. Also in agreement with our previous observations, the abundance of mRNAs associated with reduced body si...Continue Reading

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Citations

May 16, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dipsikha BiswasThomas Pulinilkunnil
Oct 17, 2017·Current Opinion in Clinical Nutrition and Metabolic Care·Daniela Salinas-RubioLilia G Noriega
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Aug 7, 2021·Frontiers in Physiology·Gagandeep MannOlasunkanmi A J Adegoke
Sep 21, 2021·Critical Reviews in Food Science and Nutrition·Elżbieta SupruniukAdrian Chabowski

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