Depletion of branched‐chain aminotransferase 2 (BCAT2) enzyme impairs myoblast survival and myotube formation

Dhanani, Zameer; Mann, G. S.; Adegoke, Olasunkanmi A. J.

doi:10.14814/phy2.14299

Cited by 9 publications

(10 citation statements)

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“…It would be interesting to see the effects of muscle specific deletion of BCAT2 on skeletal muscle and whole-body metabolism. Interestingly, myoblasts depleted of BCAT2 are impaired in their ability to form myotubes ( Dhanani et al, 2019 ).…”

Section: Bcat2 and Its Regulation In Skeletal Musclementioning

confidence: 99%

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

et al. 2021

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Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism and energy homeostasis. They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication for macronutrient metabolism. However, elevated circulating levels of BCAAs and of their ketoacids as well as impaired catabolism of these amino acids (AAs) are implicated in the development of insulin resistance and its sequelae, including type 2 diabetes, cardiovascular disease, and of some cancers, although other studies indicate supplements of these AAs may help in the management of some chronic diseases. Here, we first reviewed the catabolism of these AAs especially in skeletal muscle as this tissue contributes the most to whole body disposal of the BCAA. We then reviewed emerging mechanisms of control of enzymes involved in regulating BCAA catabolism. Such mechanisms include regulation of their abundance by microRNA and by post translational modifications such as phosphorylation, acetylation, and ubiquitination. We also reviewed implications of impaired metabolism of BCAA for muscle and whole-body metabolism. We comment on outstanding questions in the regulation of catabolism of these AAs, including regulation of the abundance and post-transcriptional/post-translational modification of enzymes that regulate BCAA catabolism, as well the impact of circadian rhythm, age and mTORC1 on these enzymes. Answers to such questions may facilitate emergence of treatment/management options that can help patients suffering from chronic diseases linked to impaired metabolism of the BCAAs.

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Section: Bcat2 and Its Regulation In Skeletal Musclementioning

confidence: 99%

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

et al. 2021

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“…ACSBG1 involves in S1P metabolism, which functions as a bioactive lipid molecule [ 26 ]. BCAT2 plays an important role in the production of the branched-chain amino acids; the study showed that the depletion of BCAT2 enzyme impairs myoblast survival, indicating a suppressing apoptosis property of BCAT2 [ 27 ]. Isotretinoin induced downregulated expression of ACSBG1 and BCAT2 might be related to decreased sebum production and apoptosis of sebocytes, respectively.…”

Section: Discussionmentioning

confidence: 99%

Putative Genes and Pathways Involved in the Acne Treatment of Isotretinoin via Microarray Data Analyses

Chen

et al. 2020

BioMed Research International

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Acne is the eighth most common disease worldwide. Disease burden of acne such as anxiety, reduced self-esteem, and facial scarring lowers the life quality of acne patients. Isotretinoin is the most potent treatment for moderate-severe acne. However, the adverse events of isotretinoin especially teratogenicity limit its use. This study aims at investigating the therapeutical mechanisms of isotretinoin using bioinformatics analysis. Differentially expressed genes (DEGs) were filtered from microarray datasets GSE10432, GSE10433, and GSE11792. Functional and pathway enrichment analyses of DEGs were performed. Protein–protein interaction (PPI) network and module analyses were also conducted based on DEGs. Using isotretinoin for 1 week, LCN2, PTGES, and GDF15 were upregulated and might mediate sebocytes apoptosis and thus decreased sebum production; CCL2 originated from activated TNF signaling pathway and S100A7 could be related with “acne-flare”. While treating with isotretinoin for 8 weeks, key genes were downregulated, including HMGCS1, HMGCR, FDFT1, MVD, IDI1, and FDPS, which may be associated with decreased sebum synthesis; HMGCS1, HMGCR, and FDFT1 also probably associated with apoptosis of sebocytes. There were only two common genes including ACSBG1 and BCAT2 which worked in both 1 week and 8 weeks and could associate with decreased sebum synthesis and apoptosis of sebocytes, respectively. These results indicate potential therapeutics and side effect mechanisms of isotretinoin in the acne treatment and provide a research direction to further investigate the therapeutic mechanism of isotretinoin and thus develop retinoid-like compounds with similar curative effect and without teratogenicity.

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“…This dimer catalyzes the rst step in the production of branched-chain amino acids, such as leucine, isoleucine and valine. The abnormal expression of BCAT2 also affects cell proliferation and differentiation [73]. ASNS-encoded proteins are involved in the synthesis of asparagine [74].…”

Section: Discussionmentioning

confidence: 99%

Identification of regulatory networks and hub genes controlling mammary gland development and lactation in dairy goats during the late lactation, dry period, and late gestation stages

Xuan

Chao

Zhao

et al. 2020

Preprint

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Background From the late lactation to late gestation stages, the mammary gland tissue of goats undergoes a process from involution to remodeling and then to high differentiation of mammary gland tissue. From the perspective of lactation, this is a continuous development process of the goat mammary gland from the termination of lactation to the restoration of lactation. We performed transcriptome sequencing on goat mammary gland tissues at three mammary gland developmental stages to screen for differentially expressed genes that affect mammary gland development and the physiological process of lactation and mapped their expression profiles in three stages. The objective of this study is to reveal the expression characteristics of these genes and their potential function during mammary gland development and lactation. Results We identified 1,381 differentially expressed genes in the mammary gland during three stages and found that the expression level of genes encoding casein, such as alpha-s1-casein (CSN1S1), alpha-s2-casein (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3), and alpha-lactalbumin (LALBA) were higher in mammary gland tissues during the late lactation stage and late gestation stage than those during the dry period. In addition, we constructed six functional networks related to differentially expressed genes and found that these genes are closely related to mammary gland growth and development, apoptosis, immunity, substance transport, biosynthesis, and metabolism. Finally, we identified 35 differentially expressed transcription factors, which were classified into 16 families, and predicted that transcription factors of the basic leucine zipper domain (bZIP) family and basic helix-loop-helix (bHLH) family regulated the expression levels of genes related to mammary gland development and lactation. Conclusions Among the late lactation, dry period, and late gestation stages, there are differences in the expression levels of genes related to mammary gland growth and development, apoptosis, immunity, basic substance transport, biosynthesis, and metabolism in mammary gland tissues. Some genes in the same family or with similar functions have similar expression patterns. These differentially expressed genes or transcription factors work synergistically to participate in the regulation of mammary gland development and the physiological process of lactation.

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Depletion of branched‐chain aminotransferase 2 (BCAT2) enzyme impairs myoblast survival and myotube formation

Cited by 9 publications

References 50 publications

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Putative Genes and Pathways Involved in the Acne Treatment of Isotretinoin via Microarray Data Analyses

Identification of regulatory networks and hub genes controlling mammary gland development and lactation in dairy goats during the late lactation, dry period, and late gestation stages

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