Branched-chain amino acids regulate intracellular protein turnover in porcine mammary epithelial cells

Rezaei, Reza; Wu, Guoyao

doi:10.1007/s00726-022-03203-y

Cited by 6 publications

(6 citation statements)

References 70 publications

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“…37 Branched-chain AAs can increase milk protein synthesis via inhibiting the ubiquitin− proteasome pathway. 38 Previous studies have shown that ubiquitin chains can be assembled on the N-terminal Met in peptides, termed Met1-linked ubiquitin chains, which is a basic signaling pathway that regulates cell physiology. 39 BRCC36 is a K63-linkage specific deubiquitinase, and there has been no report on Met1-linked ubiquitination regulated by BRCC36.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The regulation of glucose on milk lipid synthesis in bovine MECs is mediated by the ubiquitin–proteasome system . Branched-chain AAs can increase milk protein synthesis via inhibiting the ubiquitin–proteasome pathway . Previous studies have shown that ubiquitin chains can be assembled on the N-terminal Met in peptides, termed Met1-linked ubiquitin chains, which is a basic signaling pathway that regulates cell physiology .…”

Section: Discussionmentioning

confidence: 99%

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Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Xie,

Li,

Zhang

et al. 2024

J. Agric. Food Chem.

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Methionine (Met) functions as a key stimulator on the mTOR signaling pathway and milk synthesis, but the molecular mechanism remains incompletely understood. We investigated the regulatory roles of BRCC36 in Met-stimulated milk lipid and protein synthesis, cell proliferation, and the mTOR signaling pathway. Knockdown of BRCC36 promoted milk lipid and protein synthesis in HC11 cells as well as cell proliferation by increasing the levels of mTOR gene transcription and protein phosphorylation. Conversely, the gene activation of BRCC36 had opposite effects. Furthermore, BRCC36 gene activation completely blocked Met stimulation on the BRG1 protein level and mTOR mRNA level and protein phosphorylation. BRCC36 bound to BRG1, and BRCC36 and BRG1 bound to the same region on the mTOR promoter. BRCC36 inhibited the BRG1 protein level and the binding of BRG1 to the mTOR promoter. Met decreased the BRCC36 protein level, and this effect was significantly attenuated by MG132 but not affected by cycloheximide or chloroquine. We further showed that Met increased BRCC36 ubiquitination degradation. Our findings reveal that Met promotes milk lipid and protein synthesis in MECs through the BRCC36-BRG1-mTOR signaling axis.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Xie,

Li,

Zhang

et al. 2024

J. Agric. Food Chem.

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“…The activation of the mTOR pathway closely links to amino acid (AA) levels. It has been proven that AAs, particularly branched-chain amino acids (BCAAs), regulate protein synthesis through the mTOR pathway by controlling S6K1 and 4E-BP1 activities (62,63). Leucine, the primary BCAA that regulates protein synthesis, accelerates protein synthesis in the organism by activating the mTOR pathway, thereby promoting growth (20,64,65).…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with Clostridium autoethanogenum protein improves growth performance and promotes muscle protein synthesis by activating the mTOR signaling pathway of the broiler

Shan,

Liu,

et al. 2024

Front. Vet. Sci.

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The experiment aimed to evaluate the effects of different ratios of Clostridium autoethanogenum protein (CAP) used in the diets on the growth performance, muscle quality, serum indexes, and mTOR pathway of white feather broilers. Four hundred and eighty 1-day-old Arbor Acres (AA) broilers, comprising equal numbers of males and females, were randomly assigned to one of four treatments, and each treatment consisted of 12 replicates of 10 birds. Four diets were formulated based on isoenergetic and isonitrogenous principles. The control group (CAP 0) did not receive any CAP, while the experimental groups received 2% (CAP 2), 3% (CAP 3), and 4% (CAP 4) of CAP for six weeks. Compared with the CAP0, (1) The feed conversion ratio (FCR) was lower (p < 0.05), and the leg muscle yield was higher (p < 0.05) in the CAP3 and CAP4; (2) The serum levels of TP, ALB, T-AOC, and SOD were improved in the CAP3 (p < 0.05); (3) The expression of Lipin-1 gene was down-regulated and AMPKɑ2, Akt, and 4E-BP1 genes were up-regulated in the experiment group (p < 0.05); (4) The inclusion of 3% CAP in the diet increased the levels of 4E-BP1, S6K1, Akt, and AMPKɑ2 phosphorylation by modulating the mTOR signaling pathway (p < 0.05). In conclusion, broiler diets containing 3% CAP can activate the mTOR signaling pathway to promote muscle synthesis and improve growth performance.

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“…days). 55 Furthermore, there is a suggestion that the catabolism of branched-chain AAs in BAT regulates energy homeostasis in mice. 56 Although we did not determine mitochondrial biogenesis in BAT, results of our present work indicated that oral administration of Leu did not affect the rates of oxidation of energy substrates in the BAT of lean or obese rats (Table 9).…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with L-leucine reduces nitric oxide synthesis by endothelial cells of rats

Tekwe,

Luan,

Meininger

et al. 2023

Exp Biol Med (Maywood)

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This study tested the hypothesis that elevated L-leucine concentrations in plasma reduce nitric oxide (NO) synthesis by endothelial cells (ECs) and affect adiposity in obese rats. Beginning at four weeks of age, male Sprague-Dawley rats were fed a casein-based low-fat (LF) or high-fat (HF) diet for 15 weeks. Thereafter, rats in the LF and HF groups were assigned randomly into one of two subgroups ( n = 8/subgroup) and received drinking water containing either 1.02% L-alanine (isonitrogenous control) or 1.5% L-leucine for 12 weeks. The energy expenditure of the rats was determined at weeks 0, 6, and 11 of the supplementation period. At the end of the study, an oral glucose tolerance test was performed on all the rats immediately before being euthanized for the collection of tissues. HF feeding reduced ( P < 0.001) NO synthesis in ECs by 21% and whole-body insulin sensitivity by 19% but increased ( P < 0.001) glutamine:fructose-6-phosphate transaminase (GFAT) activity in ECs by 42%. Oral administration of L-leucine decreased ( P < 0.05) NO synthesis in ECs by 14%, increased ( P < 0.05) GFAT activity in ECs by 35%, and reduced ( P < 0.05) whole-body insulin sensitivity by 14% in rats fed the LF diet but had no effect ( P > 0.05) on these variables in rats fed the HF diet. L-Leucine supplementation did not affect ( P > 0.05) weight gain, tissue masses (including white adipose tissue, brown adipose tissue, and skeletal muscle), or antioxidative capacity (indicated by ratios of glutathione/glutathione disulfide) in LF- or HF-fed rats and did not worsen ( P > 0.05) adiposity, whole-body insulin sensitivity, or metabolic profiles in the plasma of obese rats. These results indicate that high concentrations of L-leucine promote glucosamine synthesis and impair NO production by ECs, possibly contributing to an increased risk of cardiovascular disease in diet-induced obese rats.

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Branched-chain amino acids regulate intracellular protein turnover in porcine mammary epithelial cells

Cited by 6 publications

References 70 publications

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Methionine Promotes Milk Synthesis through the BRCC36-BRG1-mTOR Signaling Axis in Mammary Epithelial Cells

Dietary supplementation with Clostridium autoethanogenum protein improves growth performance and promotes muscle protein synthesis by activating the mTOR signaling pathway of the broiler

Dietary supplementation with L-leucine reduces nitric oxide synthesis by endothelial cells of rats

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