Methionine Promotes Milk Protein and Fat Synthesis and Cell Proliferation via the SNAT2-PI3K Signaling Pathway in Bovine Mammary Epithelial Cells

Qi, Hao; Meng, Chunyu; Jin, Xin; Li, Xueying; Li, Ping; Gao, Xuejun

doi:10.1021/acs.jafc.8b04241

Cited by 67 publications

(77 citation statements)

References 40 publications

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“…Once the mTOR system is activated by AA sufficiency, mTOR and its downstream molecules (S6K1 and 4EBP1) are phosphorylated (44,45) . In the study, alterations of the protein expression of mTOR-related proteins by Met supplementation were in accordance with previous findings in BMEC supplemented with Met (29,42) . However, we found that SARS knockdown depressed mTOR activation under Met stimulation, which is consistent with the inhibition of the mTOR activation by leucyl-tRNA synthetase knockdown in the HEK293T cells (22) and BMEC (23) in response to leucine.…”

Section: Discussionsupporting

confidence: 92%

“…Studies reported that the lactation performance (especially the yield of milk and milk protein and milk protein concentration) in dairy cows receiving supplemental dietary Met (25-35 g/d) at early lactation (39) or postruminal infusion of rumen-protected Met (60 g/d) during the peripartal period in vivo (40) was both significantly increased compared with those in groups without Met supplementation. Our study showed that Met supplementation at the concentration of 0•6 mM can significantly promote the casein synthesis and activate mTOR signalling, which were similar to several previous studies (29,41,42) .…”

Section: Discussionsupporting

confidence: 91%

“…The previous study (29) and the supplementary materials in the present study showed that Met supplementation at the concentration of 0•6 mM enhanced the BMEC viability and β-casein synthesis at the highest levels. Therefore, in the present study, we selected 0•6 mM Met to treat the BMEC.…”

Section: Experimental Design and Treatmentssupporting

confidence: 68%

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Seryl-tRNA synthetase is involved in methionine stimulation of β-casein synthesis in bovine mammary epithelial cells

et al. 2019

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Despite the well-characterised mechanisms of amino acids (AA) regulation of milk protein synthesis in mammary glands (MG), the underlying specific AA regulatory machinery in bovine MG remains further elucidated. As methionine (Met) is one of the most important essential and limiting AA for dairy cows, it is crucial to expand how Met exerts its regulatory effects on dairy milk protein synthesis. Our previous work detected the potential regulatory role of seryl-tRNA synthetase (SARS) in essential AA (EAA)-stimulated bovine casein synthesis. Here, we investigated whether and how SARS participates in Met stimulation of casein production in bovine mammary epithelial cells (BMEC). With or without RNA interference against SARS, BMEC were treated with the medium in the absence (containing all other EAA and devoid of Met alone)/presence (containing 0·6 mm of Met in the medium devoid of Met alone) of Met. The protein abundance of β-casein and members of the mammalian target of rapamycin (mTOR) and general control nonderepressible 2 (GCN2) pathways was determined by immunoblot assay after 6 h treatment, the cell viability and cell cycle progression were determined by cell counting and propidium iodide-staining assay after 24 h treatment, and protein turnover was determined by l-[ring-3H5]phenylalanine isotope tracing assay after 48 h treatment. In the absence of Met, there was a general reduction in cell viability, total protein synthesis and β-casein production; in contrast, total protein degradation was enhanced. SARS knockdown strengthened these changes. Finally, SARS may work to promote Met-stimulated β-casein synthesis via affecting mTOR and GCN2 routes in BMEC.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

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Seryl-tRNA synthetase is involved in methionine stimulation of β-casein synthesis in bovine mammary epithelial cells

et al. 2019

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“…Additional nutritional compounds beside FA can regulate SREBP1 in bovine mammary epithelial cells, such as methionine [277] which is partly mediated by FABP5 [278]. Alongside milk fat synthesis, SREBP1 plays other roles in dairy cows, such as the demonstrated role in regulating homeostasis of the sodium/iodide symporter in mammary epithelial cells, as observed in humans [279], and it is involved in liver lipid metabolism in peripartum cows [263], including regulation of TAG synthesis in bovine hepatocytes [280,281].…”

Section: Sterol Regulatory Element-binding Proteinsmentioning

confidence: 99%

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

Bionaz

Vargas‐Bello‐Pérez

Busato

2020

J Animal Sci Biotechnol

104

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High producing dairy cows generally receive in the diet up to 5–6% of fat. This is a relatively low amount of fat in the diet compared to diets in monogastrics; however, dietary fat is important for dairy cows as demonstrated by the benefits of supplementing cows with various fatty acids (FA). Several FA are highly bioactive, especially by affecting the transcriptome; thus, they have nutrigenomic effects. In the present review, we provide an up-to-date understanding of the utilization of FA by dairy cows including the main processes affecting FA in the rumen, molecular aspects of the absorption of FA by the gut, synthesis, secretion, and utilization of chylomicrons; uptake and metabolism of FA by peripheral tissues, with a main emphasis on the liver, and main transcription factors regulated by FA. Most of the advances in FA utilization by rumen microorganisms and intestinal absorption of FA in dairy cows were made before the end of the last century with little information generated afterwards. However, large advances on the molecular aspects of intestinal absorption and cellular uptake of FA were made on monogastric species in the last 20 years. We provide a model of FA utilization in dairy cows by using information generated in monogastrics and enriching it with data produced in dairy cows. We also reviewed the latest studies on the effects of dietary FA on milk yield, milk fatty acid composition, reproduction, and health in dairy cows. The reviewed data revealed a complex picture with the FA being active in each step of the way, starting from influencing rumen microbiota, regulating intestinal absorption, and affecting cellular uptake and utilization by peripheral tissues, making prediction on in vivo nutrigenomic effects of FA challenging.

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“…Increasing evidence suggests that Cyclin D1 level decreases in response to cell cycle arrest, affecting cell homeostasis and resulting in the termination of various cellular processes [26,27]. In previous studies, percentages of cells in the S or G2/M phases increased, while cell proliferation decreased with a decrease in Cyclin D1 level, ultimately affecting milk protein and fat synthesis [28,29]. In our study, loss of UFL1 induced a decrease in Cyclin D1 level and an increase in the rate of apoptosis, thereby disrupting homeostasis of mammary epithelial cells.…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 93%

UFM1-Specific Ligase 1 Ligating Enzyme 1 Mediates Milk Protein and Fat Synthesis-Related Gene Expression via the JNK Signaling Pathway in Mouse Mammary Epithelial Cells

Kuang

Yang

Lian

et al. 2020

Oxidative Medicine and Cellular Longevity

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Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) has been characterized as a ubiquitin-like (Ubl) protein that affects a range of cellular processes across various pathways. In this study, mouse mammary epithelial cells (HC11 cell line) and UFL1 knockout (KO) mice were used to establish UFL1 knockdown models to explore the influence of UFL1 on milk protein and fat synthesis in the mouse mammary gland and the underlying mechanisms. This is the first study to show UFL1 localization in mouse mammary epithelial cells. UFL1 depletion by transfected UFL1 siRNA (siUFL1) caused aggravated apoptosis. In addition, UFL1 depletion suppressed milk protein synthesis-related protein level in vivo and in vitro. Conversely, ACACA and FASN expressions increased in UFL1-deficient mice. Moreover, UFL1 depletion increased triglyceride synthesis levels and inhibited the p-JNK expression. Importantly, the expression of proteins related to milk protein synthesis was decreased in JNK- and UFL1-deficient cells, whereas proteins related to milk fat synthesis showed the opposite trend, indicating that UFL1 affects milk protein and fat synthesis via the suppression of JNK activation. Overall, our findings indicate that UFL1 plays a key role in mammary milk and fat synthesis via JNK activation.

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Methionine Promotes Milk Protein and Fat Synthesis and Cell Proliferation via the SNAT2-PI3K Signaling Pathway in Bovine Mammary Epithelial Cells

Cited by 67 publications

References 40 publications

Seryl-tRNA synthetase is involved in methionine stimulation of β-casein synthesis in bovine mammary epithelial cells

Seryl-tRNA synthetase is involved in methionine stimulation of β-casein synthesis in bovine mammary epithelial cells

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

UFM1-Specific Ligase 1 Ligating Enzyme 1 Mediates Milk Protein and Fat Synthesis-Related Gene Expression via the JNK Signaling Pathway in Mouse Mammary Epithelial Cells

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