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Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver.
Toxicol Mech Methods. 2020 Jul; 30(6):407-416.TM

Abstract

Mitogen-activated protein kinases (MAPKs) are versatile proteins that have been suggested to be involved in the regulation of lipid metabolism. This study was designed to investigate the responses of MAPK signaling to chronic ethanol exposure in vivo and in vitro, and try to explore its role in the pathogenesis of alcoholic fatty liver (AFL). Mice were fed with Lieber-Decarli liquid diet (5% ethanol, w/v) for 4 weeks to induce fatty liver, and the chronological changes of MAPK phosphorylation were measured using western blotting. We found that chronic ethanol feeding led to accumulation of triglyceride (TG), decreased phosphorylation of MAPKs, decreased protein level of peroxisomal proliferator activation receptor α (PPARα), and increased protein expression of cytochrome P4502E1 (CYP2E1) in mice liver. In vitro study showed that overexpression of CYP2E1 blunted the response of MAPKs to ethanol, and MAPK phosphatase 1 (MKP-1) knockdown by siRNA led to upregulation of PPARα protein level. Lastly, epidermal growth factor (EGF), a well-known MAPK activator, significantly suppressed chronic ethanol-induced hepatic fat accumulation and decline of PPARα expression in mice liver. Collectively, MAPK suppression, possibly due to the activation of hepatic CYP2E1, may be involved in chronic ethanol-induced hepatic steatosis.

Authors+Show Affiliations

Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, China.Institute of Toxicology, School of Public Health, Shandong University, Jinan, China.Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, China.Institute of Toxicology, School of Public Health, Shandong University, Jinan, China.Department of Orthopaedic Surgery, Qilu Hospital of Shandong University, Jinan, China.Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32237978

Citation

Guo, Fang-Fang, et al. "Downregulation of Mitogen-activated Protein Kinases (MAPKs) in Chronic Ethanol-induced Fatty Liver." Toxicology Mechanisms and Methods, vol. 30, no. 6, 2020, pp. 407-416.
Guo FF, Xiao M, Wang SY, et al. Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020;30(6):407-416.
Guo, F. F., Xiao, M., Wang, S. Y., Zeng, T., Cheng, L., & Xie, Q. (2020). Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicology Mechanisms and Methods, 30(6), 407-416. https://doi.org/10.1080/15376516.2020.1747126
Guo FF, et al. Downregulation of Mitogen-activated Protein Kinases (MAPKs) in Chronic Ethanol-induced Fatty Liver. Toxicol Mech Methods. 2020;30(6):407-416. PubMed PMID: 32237978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. AU - Guo,Fang-Fang, AU - Xiao,Mo, AU - Wang,Shao-Yi, AU - Zeng,Tao, AU - Cheng,Lei, AU - Xie,Qing, Y1 - 2020/04/01/ PY - 2020/4/3/pubmed PY - 2021/4/1/medline PY - 2020/4/3/entrez KW - Alcoholic fatty liver KW - cytochrome P4502E1 KW - epidermal growth factor KW - mitogen-activated protein kinases KW - peroxisomal proliferator activation receptor α SP - 407 EP - 416 JF - Toxicology mechanisms and methods JO - Toxicol Mech Methods VL - 30 IS - 6 N2 - Mitogen-activated protein kinases (MAPKs) are versatile proteins that have been suggested to be involved in the regulation of lipid metabolism. This study was designed to investigate the responses of MAPK signaling to chronic ethanol exposure in vivo and in vitro, and try to explore its role in the pathogenesis of alcoholic fatty liver (AFL). Mice were fed with Lieber-Decarli liquid diet (5% ethanol, w/v) for 4 weeks to induce fatty liver, and the chronological changes of MAPK phosphorylation were measured using western blotting. We found that chronic ethanol feeding led to accumulation of triglyceride (TG), decreased phosphorylation of MAPKs, decreased protein level of peroxisomal proliferator activation receptor α (PPARα), and increased protein expression of cytochrome P4502E1 (CYP2E1) in mice liver. In vitro study showed that overexpression of CYP2E1 blunted the response of MAPKs to ethanol, and MAPK phosphatase 1 (MKP-1) knockdown by siRNA led to upregulation of PPARα protein level. Lastly, epidermal growth factor (EGF), a well-known MAPK activator, significantly suppressed chronic ethanol-induced hepatic fat accumulation and decline of PPARα expression in mice liver. Collectively, MAPK suppression, possibly due to the activation of hepatic CYP2E1, may be involved in chronic ethanol-induced hepatic steatosis. SN - 1537-6524 UR - https://www.unboundmedicine.com/medline/citation/32237978/Downregulation_of_mitogen_activated_protein_kinases__MAPKs__in_chronic_ethanol_induced_fatty_liver_ L2 - https://www.tandfonline.com/doi/full/10.1080/15376516.2020.1747126 DB - PRIME DP - Unbound Medicine ER -