Choline attenuates heat stress-induced oxidative injury and apoptosis in bovine mammary epithelial cells by modulating PERK/Nrf-2 signaling pathway

Yang, Min; Kuang, Meiqian; Wang, Genlin; Ali, Ilyas; Tang, Yujie; Yang, Caixia; Li, Yanan; Li, Lian

doi:10.1016/j.molimm.2021.05.002

Cited by 25 publications

(20 citation statements)

References 40 publications

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“…Additional information was gained in the pathway analysis concerning choline involvement in "Glycine, serine and threonine metabolism" and "Glycerophospholipid metabolism", which augments our earlier discussion about the unique multifaceted properties of choline in heat-stressed bGC protection and subsequent cell proliferation. These claims are in accordance with prior studies where choline was able to protect heat-stressed cells [74], and granulosa cells were able to recover from acute and chronic heat stress [32]. The second important metabolite we want to discuss here is uraconic acid, involved in the "Pyrimidine and Histidine metabolism" pathway.…”

Section: Discussionsupporting

confidence: 85%

Investigation of Metabolome Underlying the Biological Mechanisms of Acute Heat Stressed Granulosa Cells

Sammad

Luo

et al. 2022

IJMS

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Heat stress affects granulosa cells and the ovarian follicular microenvironment, ultimately resulting in poor oocyte developmental competence. This study aims to investigate the metabo-lomics response of bovine granulosa cells (bGCs) to in vitro acute heat stress of 43 °C. Heat stress triggers oxidative stress-mediated apoptosis in cultured bGCs. Heat-stressed bGCs exhibited a time-dependent recovery of proliferation potential by 48 h. A total of 119 metabolites were identified through LC–MS/MS-based metabolomics of the spent culture media, out of which, 37 metabolites were determined as differentially involved in metabolic pathways related to bioenergetics support mechanisms and the physical adaptations of bGCs. Multiple analyses of metabolome data identified choline, citric acid, 3-hydroxy-3-methylglutaric acid, glutamine, and glycocyamine as being upregulated, while galactosamine, AICAR, ciliatine, 16-hydroxyhexadecanoic acid, lysine, succinic acid, uridine, xanthine, and uraconic acid were the important downregulated metabolites in acute heat stress. These differential metabolites were implicated in various important metabolic pathways directed towards bioenergetics support mechanisms including glycerophospholipid metabolism, the citrate cycle (TCA cycle), glyoxylate and dicarboxylate metabolism, and serine, threonine, and tyrosine metabolism. Our study presents important metabolites and metabolic pathways involved in the adaptation of bGCs to acute heat stress in vitro.

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Section: Discussionsupporting

confidence: 85%

Investigation of Metabolome Underlying the Biological Mechanisms of Acute Heat Stressed Granulosa Cells

Sammad

Luo

et al. 2022

IJMS

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“…For the intracellular metabolomics analysis, cells were incubated in a culture dish (1.8 × 10 6 cells, 100 mm) until they reached 80% to 90% confluence. Then cells were incubated at different temperatures (37 and 42 °C [ 20 , 21 ]) after serum-free starvation overnight. Finally, MAC-T cells were collected into 15 mL tubes and stored at −80 °C until metabolomics analyses were performed.…”

Section: Methodsmentioning

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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“…Studies have shown that tert-Butylhydroquinone and resveratrol promote the nuclear translocation of Nrf2 and increase expressions of Nrf2, HO-1, and Txnrd1, thus protecting dairy mammary epithelial cells from oxidative stress induced by high temperatures and hydrogen peroxide [ 44 , 45 ], which are consistent with the present results. However, there are also research findings that show that choline protects bovine mammary epithelial cells from HS-induced oxidative stress by inhibiting the expression and nuclear translocation of Nrf2 [ 46 ]. Similarly, PB2 was reported to protect mice cerebral cortex neurons from cypermethrin-induced oxidative stress by reducing Nrf2 expression and nuclear translocation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells

Wang

Hao²,

Li³

et al. 2022

IJMS

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The objective of this study was to investigate the protective effects and potential molecular mechanisms of procyanidin B2 (PB2) in MAC-T (mammary alveolar cells-large T antigen) cells during heat stress (HS). The MAC-T cells were divided into three treatment groups: control (37 °C), HS (42 °C), and PB2 + HS (42 °C). Compared with MAC-T cells that were consistently cultured at 37 °C, acute HS treatment remarkably decreased cell viability, reduced activities of catalase (CAT), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and elevated intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS). Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2) was activated and translocated to the nucleus, in accompaniment with upregulation of Nrf2, heme oxygenase 1 (HO-1), thioredoxin reductase 1 (Txnrd1), and heat shock protein 70 (HSP70). In parallel, both mRNA transcript and actual protein secretion of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were increased by heat stress. Pretreatment of MAC-T cells with 0~25 μM PB2 alleviated the decline of cell viability by HS in a dose-dependent fashion and protected cells against HS-induced oxidative stress, as evidenced by significantly improved CAT, SOD, and T-AOC activity, as well as with decreased MDA and ROS generation. Furthermore, PB2 further activated the Nrf2 signaling pathway and reversed the inflammatory response induced by HS. Silencing of Nrf2 by si-Nrf2 transfection not only exacerbated HS-induced cell death and provoked oxidative stress and the inflammatory response, but also greatly abolished the cytoprotective effects under HS of PB2. In summary, PB2 protected MAC-T cells against HS-induced cell death, oxidative stress, and inflammatory response, partially by operating at the Nrf2 signal pathway.

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Choline attenuates heat stress-induced oxidative injury and apoptosis in bovine mammary epithelial cells by modulating PERK/Nrf-2 signaling pathway

Cited by 25 publications

References 40 publications

Investigation of Metabolome Underlying the Biological Mechanisms of Acute Heat Stressed Granulosa Cells

Investigation of Metabolome Underlying the Biological Mechanisms of Acute Heat Stressed Granulosa Cells

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

Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells

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