title: Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells.
abstract: Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP) on hydrogen peroxide (H₂O₂)-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H₂O₂-induced intracellular reactive oxygen species (ROS) generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1) expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2), which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China. 13126750913@163.com.|College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing 100083, China. 13126750913@163.com.
authors.forename: Tiange
authors.initials: T
authors.lastname: Li
authors.affiliation: Key Laboratory of Space Nutrition and Food Engineering, China Astronaut Training Center, Beijing 100094, China. chenb12@aliyun.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA. min.du@wsu.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Du
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China. songjiajia1208@126.com.|College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing 100083, China. songjiajia1208@126.com.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Song
authors.affiliation: College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing 100083, China. chengxue_604@163.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Cheng
authors.affiliation: College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing 100083, China. xuxuwang@foxmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100083, China. maoxueying@cau.edu.cn.|College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Ministry of Education, China Agricultural University, Beijing 100083, China. maoxueying@cau.edu.cn.
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002364:Caseins / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004790:Enzyme Induction; D051547:Heme Oxygenase-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011492:Protein Hydrolysates / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002364:Caseins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010446:Peptide Fragments; D011492:Protein Hydrolysates; D017382:Reactive Oxygen Species; C065989:caseinomacropeptide; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: ERK1/2; HO-1; Nrf2; casein glycomacropeptide; oxidative stress; p38 MAPK