mTOR Signaling in Metabolic Stress Adaptation

Wu, Cheng-Wei; Storey, Kenneth B.

doi:10.3390/biom11050681

Cited by 28 publications

(27 citation statements)

References 85 publications

(130 reference statements)

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“…AKT , TSC1 , TSC2 and RHEB are the key upstream signaling molecules that regulate the activity of the mTOR pathway, and EIF4EBP1 , eIF4E , eEF2K and eEF2 are the important downstream regulators of the mTOR pathway [ 74 ]. For the upstream activity of mTOR, AKT and RHEB are the positive regulators of mTOR, and TSC1 and TSC2 are the negative regulators of mTOR [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Zhang

Liu

et al. 2021

Animals

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Heat stress (HS) is one of the most serious factors to negatively affect the lactation performance of dairy cows. Bovine mammary epithelial cells are important for lactation. It was demonstrated that HS decreases the lactation performance of dairy cows, partly through altering gene expression within bovine mammary epithelial tissue. However, the cellular metabolism mechanisms under HS remains largely unknown. The objective of this study was to determine whether HS induced changes in intracellular metabolites and gene transcription related to amino acid metabolism, amino acid transportation and the mTOR signaling pathway. Immortalized bovine mammary epithelial cell lines (MAC-T cells, n = 5 replicates/treatment) were incubated for 12 h at 37 °C (Control group) and 42 °C (HS group). Relative to the control group, HS led to a greater mRNA expression of heat shock protein genes HSF1, HSPB8, HSPA5, HSP90AB1 and HSPA1A. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 417 differential metabolites with p < 0.05 and a variable importance in projection (VIP) score >1.0 in the HS group. HS resulted in significant changes to the intracellular amino acid metabolism of glutathione, phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, arginine, proline, cysteine, methionine, alanine, aspartate and glutamate. HS led to a greater mRNA expression of the amino acid transporter genes SLC43A1, SLC38A9, SLC36A1, and SLC3A2 but a lower mRNA expression of SLC7A5 and SLC38A2. Additionally, HS influenced the expression of genes associated with the mTOR signaling pathway and significantly upregulated the mRNA expression of mTOR, AKT, RHEB, eIF4E and eEF2K but decreased the mRNA expression of TSC1, TSC2 and eEF2 relative to the control group. Compared with the control group, HS also led to greater mRNA expression of the CSN1S2 gene. Overall, our study indicates that bovine mammary epithelial cells may have the ability to resist HS damage and continue milk protein synthesis partly through enhanced intracellular amino acid absorption and metabolism and by activating the mTOR signaling pathway during HS.

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Section: Discussionmentioning

confidence: 99%

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Zhang

Liu

et al. 2021

Animals

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“…Rapamycin (mTOR) production was also enhanced, with its relative abundance rising from 865 in CK to 1253, 1953, and 1249 in UV-10, UV-20, and UV-30, respectively. The mTOR is regularly employed as a signaling, signaling stimulus, and immune regulator in different metabolic stress adaptations [ 35 ]. The mTOR regulates many processes required for cell growth and metabolism in the BSF, integrating cellular nutrition and stress status and inducing appropriate cellular responses.…”

Section: Discussionmentioning

confidence: 99%

Food Waste Management Employing UV-Induced Black Soldier Flies: Metabolomic Analysis of Bioactive Components, Antioxidant Properties, and Antibacterial Potential

Guo

Muhmood

et al. 2022

IJERPH

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Food waste, as a major part of municipal solid waste, has been increasingly generated worldwide. Efficient and feasible utilization of this waste material for biomanufacturing is crucial to improving economic and environmental sustainability. In the present study, black soldier flies (BSF) larvae were used as carriers to treat and upcycle food waste. Larvae of the BSF were incubated with UV light for 10, 20, and 30 min at a wavelength of 257.3 nm and an intensity of 8 W. The food waste utilization efficiency, antioxidant assays, antibacterial activity, and bioactive metabolites without and with UV treatment were determined and compared. Results showed that the BSF larvae feed utilization rate was around 75.6%, 77.7%, and 71.2% after UV treatment for 10, 20, and 30 min respectively, contrasting with the non-UV induced group (73.7%). In addition, it was perceived that the UV exposure enhanced antioxidant and antimicrobial properties of BSF extracts, and the maximum values were observed after 20 min UV induction time. Moreover, UV-induced BSF extracts showed an improved metabolic profile than the control group, with a change in the amino acids, peptides, organic acids, lipids, organic oxides, and other derivatives. This change in metabolomics profile boosted environmental signaling, degradation of starch, amino acids, sugars, and peptide metabolism. It was concluded that the bioconversion of food wastes using UV-induced BSF larvae can enhance the generation of a variety of functional proteins and bioactive compounds with potent antioxidant and antimicrobial activity. However, more studies are required to exploit the efficiency of UV treatment in improving BSF’s potential for upcycling of food wastes.

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“…mTOR is an atypical serine/threonine kinase that exists as mTOR complex 1 (mTORC1) and mTORC2 ( 65 ). Raptor is the key scaffolding protein responsible for the recruitment of mTOR substrates to mTORC1 ( 66 , 67 ). mTORC1 is an important downstream signaling molecule that can be activated by AMPK.…”

Section: Oxidative Stress- Related Pathwaysmentioning

confidence: 99%

“…mTORC1 is an important downstream signaling molecule that can be activated by AMPK. A number of molecules downstream of mTOR have been identified, including ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E-binding protein 1, TFEB, PPARα/γ, HIF-1, PGC- 1α, and SREBP-1 ( 67 ). Indeed, there are two common pathways for AMPK/mTOR signaling transduction.…”

Section: Oxidative Stress- Related Pathwaysmentioning

confidence: 99%

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

Peng

et al. 2022

Front. Endocrinol.

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Diabetes is a chronic metabolic disease that is increasing in prevalence and causes many complications. Diabetic cardiomyopathy (DCM) is a complication of diabetes that is associated with high mortality, but it is not well defined. Nevertheless, it is generally accepted that DCM refers to a clinical disease that occurs in patients with diabetes and involves ventricular dysfunction, in the absence of other cardiovascular diseases, such as coronary atherosclerotic heart disease, hypertension, or valvular heart disease. However, it is currently uncertain whether the pathogenesis of DCM is directly attributable to metabolic dysfunction or secondary to diabetic microangiopathy. Oxidative stress (OS) is considered to be a key component of its pathogenesis. The production of reactive oxygen species (ROS) in cardiomyocytes is a vicious circle, resulting in further production of ROS, mitochondrial DNA damage, lipid peroxidation, and the post-translational modification of proteins, as well as inflammation, cardiac hypertrophy and fibrosis, ultimately leading to cell death and cardiac dysfunction. ROS have been shown to affect various signaling pathways involved in the development of DCM. For instance, OS causes metabolic disorders by affecting the regulation of PPARα, AMPK/mTOR, and SIRT3/FOXO3a. Furthermore, OS participates in inflammation mediated by the NF-κB pathway, NLRP3 inflammasome, and the TLR4 pathway. OS also promotes TGF-β-, Rho-ROCK-, and Notch-mediated cardiac remodeling, and is involved in the regulation of calcium homeostasis, which impairs ATP production and causes ROS overproduction. In this review, we summarize the signaling pathways that link OS to DCM, with the intention of identifying appropriate targets and new antioxidant therapies for DCM.

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mTOR Signaling in Metabolic Stress Adaptation

Cited by 28 publications

References 85 publications

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Food Waste Management Employing UV-Induced Black Soldier Flies: Metabolomic Analysis of Bioactive Components, Antioxidant Properties, and Antibacterial Potential

Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy

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