Niacin Alleviates Dairy Cow Mastitis by Regulating the GPR109A/AMPK/NRF2 Signaling Pathway

Guo, Wenjin; Liu, Juxiong; Li, Wen; Ma, He; Gong, Qian; Kan, Xingchi; Cao, Yu; Wang, Jianfa; Fu, Shoupeng

doi:10.3390/ijms21093321

Cited by 30 publications

(14 citation statements)

References 52 publications

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“…Work with non-ruminants confirmed that NFE2L2 activates autophagy through the control of LAMP2A transcription, which alleviates oxidative stress by inhibiting accumulation of oxidized protein aggregates [ 17 ]. Interestingly, the regulation of autophagy via NFE2L2 also was confirmed in primary bovine mammary epithelial cells [ 18 ]. Thus, NFE2L2-mediated autophagy might play a protective role against oxidative stress in bovine mammary epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids

Chang

Sun

Jia

et al. 2022

J Animal Sci Biotechnol

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Background In early lactation, bovine mammary epithelial cells undergo serious metabolic challenges and oxidative stress both of which could be alleviated by activation of autophagy. Nuclear factor erythroid 2 related factor 2 (NFE2L2), a master regulator of cellular redox homeostasis, plays an important role in the regulation of autophagy and oxidative stress. Thus, the objective of this study was to investigate the role of NFE2L2-mediated autophagy on oxidative stress of bovine mammary epithelial cells in response to exogenous free fatty acids (FFA). Results Exogenous FFA induced linear and quadratic decreases in activities of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD), and increases in the contents of reactive oxygen species (ROS) and malondialdehyde (MDA). Protein abundance of LC3-phosphatidylethanolamine conjugate (LC3-II) and the number of autophagosomes and autolysosomes decreased in a dose-dependent manner, while protein abundance of p62 increased in cells challenged with FFA. Activation of autophagy via pre-treatment with Rap attenuated the FFA-induced ROS accumulation. Importantly, FFA inhibited protein abundance of NFE2L2 and the translocation of NFE2L2 into the nucleus. Knockdown of NFE2L2 by siRNA decreased protein abundance of LC3-II, while it increased protein abundance of p62. Furthermore, sulforaphane (SFN) pre-treatment attenuated the FFA-induced oxidative stress by activating NFE2L2-mediated autophagy. Conclusions The data suggested that NFE2L2-mediated autophagy is an important antioxidant mechanism in bovine mammary epithelial cells experiencing increased FFA loads.

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Section: Introductionmentioning

confidence: 99%

Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids

Chang

Sun

Jia

et al. 2022

J Animal Sci Biotechnol

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“…Furthermore, Zhao et al (58) found that lncRNA UCA1 could accelerate cell viability, block apoptosis and function as competitive endogenous RNA (ceRNA) to target TLR4 by sponging miR-499b-5p, thereby alleviating the LPS-challenged cell damage. Based on above results, it was speculated that these DElncRNAs are likely involved in regulating the process of bovine mastitis via their immune-related target genes (7,(59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 97%

Differential Expression Profiles of lncRNA Following LPS-Induced Inflammation in Bovine Mammary Epithelial Cells

Wang

Yang

et al. 2021

Front. Vet. Sci.

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Bovine mastitis is an inflammatory response of mammary glands caused by pathogenic microorganisms such as Escherichia coli (E. coli). As a key virulence factor of E. coli, lipopolysaccharide (LPS) triggers innate immune responses via activation of the toll-like-receptor 4 (TLR4) signaling pathway. However, the molecular regulatory network of LPS-induced bovine mastitis has yet to be fully mapped. In this study, bovine mammary epithelial cell lines MAC-T were exposed to LPS for 0, 6 and 12 h to assess the expression profiles of long non-coding RNAs (lncRNAs) using RNA-seq. Differentially expressed lncRNAs (DElncRNAs) were filtered out of the raw data for subsequent analyses. A total of 2,257 lncRNAs, including 210 annotated and 2047 novel lncRNAs were detected in all samples. A large proportion of lncRNAs were present in a high abundance, and 112 DElncRNAs were screened out at different time points. Compared with 0 h, there were 22 up- and 25 down-regulated lncRNAs in the 6 h of post-infection (hpi) group, and 27 up- and 22 down-regulated lncRNAs in the 12 hpi group. Compared with the 6 hpi group, 32 lncRNAs were up-regulated and 25 lncRNAs were down-regulated in the 12 hpi group. These DElncRNAs are involved in the regulation of a variety of immune-related processes including inflammatory responses bMECs exposed to LPS. Furthermore, lncRNA TCONS_00039271 and TCONS_00139850 were respectively significance down- and up-regulated, and their target genes involve in regulating inflammation-related signaling pathways (i.e.,Notch, NF-κB, MAPK, PI3K-Akt and mTOR signaling pathway), thereby regulating the occurrence and development of E. coli mastitis. This study provides a resource for lncRNA research on the molecular regulation of bovine mastitis

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“…In addition, BMECs, as one of the main cells of mammary tissue, are not only important immune cells, but also a major cell population for lactation in cows ( 28 , 35 ). When mastitis occurs in cows, mastitis is well known to seriously affect milk production and quality ( 11 , 19 , 34 ). Yusaku Tsugami et al.…”

Section: Discussionmentioning

confidence: 99%

“…The nuclear transcription factor Nrf-2 is considered an important regulator of cellular homeostasis; and is capable of activating the expression of a variety of cytoprotective genes ( 46 ). AMPK, as a kinase working upstream of Nrf-2, has an important role in the regulation of Nrf-2 ( 19 ). Under normal conditions, Nrf-2 exists in free form, in the cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

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Menthol Targeting AMPK Alleviates the Inflammatory Response of Bovine Mammary Epithelial Cells and Restores the Synthesis of Milk Fat and Milk Protein

et al. 2021

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Mastitis is one of the most serious diseases that causes losses in the dairy industry, seriously impairing milk production and milk quality, and even affecting human health. Menthol is a cyclic monoterpene compound obtained from the stem and leaves of peppermint, which has a variety of biological activities, including anti-inflammatory and antioxidant activity. The purpose of this study was to investigate the preventive effect of menthol on the lipopolysaccharide-induced inflammatory response in primary bovine mammary gland epithelial cells (BMECs) and its anti-inflammatory mechanism. First, BMECs were isolated and amplified from the udders of Holstein cows by enzymatic hydrolysis. BMECs were treated with menthol (10, 50, 100, 200 μM) for 1h, followed by lipopolysaccharide (5μg/ml) for 12 h. Lipopolysaccharide treatment upregulated the protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS) and the mRNA abundance of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), while menthol was able to inhibit this effect. The inhibitory effect of menthol on proinflammatory factors was significantly reduced when autophagy was blocked using 3-Methyladenine (5μg/ml), an inhibitor of autophagy. Furthermore, lipopolysaccharide treatment reduced the expression levels of milk lipids and milk proteins, which were inhibited by menthol. In addition, menthol (200 μM) treatment was able to significantly upregulate the expression level of autophagy-related protein LC3B, downregulate the expression level of P62, promote the expression abundance of autophagy-related gene mRNA, and enhance significantly enhance autophagic flux. Interestingly, treatment of BMECs with menthol (200 μM) promoted the phosphorylation of AMP-activated protein kinase (AMPK) and unc-51 like kinase 1 (ULK1) and increased the nuclear localization of nuclear factor-E2 associated factor 2 (Nrf-2). When the AMPK pathway was blocked using compound C (10μg/ml), an inhibitor of AMPK, autophagy was significantly inhibited. Autophagy levels were significantly decreased after blocking the Nrf-2 pathway using ML385 (5μg/ml), an inhibitor of Nrf-2. Overall, the data suggest that menthol activates the AMPK-ULK1 pathway to initiate the onset of autophagy and maintains the level of autophagy through the AMPK-Nrf-2 pathway. In conclusion, the findings suggest that menthol may alleviate the inflammatory response in BMECs via the AMPK/ULK1/Nrf-2/autophagy pathway.

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Niacin Alleviates Dairy Cow Mastitis by Regulating the GPR109A/AMPK/NRF2 Signaling Pathway

Cited by 30 publications

References 52 publications

Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids

Inhibiting nuclear factor erythroid 2 related factor 2-mediated autophagy in bovine mammary epithelial cells induces oxidative stress in response to exogenous fatty acids

Differential Expression Profiles of lncRNA Following LPS-Induced Inflammation in Bovine Mammary Epithelial Cells

Menthol Targeting AMPK Alleviates the Inflammatory Response of Bovine Mammary Epithelial Cells and Restores the Synthesis of Milk Fat and Milk Protein

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