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Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-κB/NLRP3 axis.
Cell Stress Chaperones. 2021 03; 26(2):387-401.CS

Abstract

Liver damage is the most severe complication of heat stress (HS). Hydrolyzed camel whey protein (CWP) possesses bioactive peptides with obviously antioxidant and anti-inflammatory activities. The current study aims to investigate whether CWP that is hydrolyzed by a simulated gastrointestinal digestion process, named S-CWP, protects BRL-3A hepatocytes from HS-induced damage via antioxidant and anti-inflammatory mechanisms. BRL-3A cells were pretreated with S-CWP before being treated at 43 °C for 1 h, and the levels of the cellular oxidative stress, inflammation, apoptosis, biomarkers for liver function, the activities of several antioxidant enzymes, and the cell viability were analyzed. The expression level of pivotal proteins in correlative signaling pathways was evaluated by western blotting. We confirmed that S-CWP alleviated HS-induced hepatocytes oxidative stress by decreased reactive oxygen species (ROS), nitric oxide (NO), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), protein carbonylation (PCO), and the activities of NADPH oxidase while enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) activities, and GSH content. S-CWP suppressed HS-induced inflammatory response by reducing the phosphorylation of NF-κB p65, the expression of NLRP3, and caspase-1 and finally alleviated caspase-3-mediated apoptosis. S-CWP also alleviated HS-induced hepatocyte injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and restoring Heat Shock Protein 70 (HSP70) expression. Furthermore, S-CWP treatment significantly enhanced the expression of NF-E2-related nuclear factor erythroid-2 (Nrf2) and HO-1. The antioxidant and anti-inflammatory effects of S-CWP were weakened by ML385, a specific Nrf2 inhibitor. Additionally, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, significantly reversed S-CWP-induced reduction in the phosphorylation of NF-κB p65. Thus, our results revealed that S-CWP protected against HS-induced hepatocytes damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NF-κB/NLRP3 axis.

Authors+Show Affiliations

Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, Hebei, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, Hebei, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China.Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. surong@imau.edu.cn. Inner Mongolia institute of Camel Research, Badain Jaran, 075131, Inner Mongolia, China. surong@imau.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33405053

Citation

Du, Donghua, et al. "Hydrolyzed Camel Whey Protein Alleviated Heat Stress-induced Hepatocyte Damage By Activated Nrf2/HO-1 Signaling Pathway and Inhibited NF-κB/NLRP3 Axis." Cell Stress & Chaperones, vol. 26, no. 2, 2021, pp. 387-401.
Du D, Lv W, Su R, et al. Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-κB/NLRP3 axis. Cell Stress Chaperones. 2021;26(2):387-401.
Du, D., Lv, W., Su, R., Yu, C., Jing, X., Bai, N., & Hasi, S. (2021). Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-κB/NLRP3 axis. Cell Stress & Chaperones, 26(2), 387-401. https://doi.org/10.1007/s12192-020-01184-z
Du D, et al. Hydrolyzed Camel Whey Protein Alleviated Heat Stress-induced Hepatocyte Damage By Activated Nrf2/HO-1 Signaling Pathway and Inhibited NF-κB/NLRP3 Axis. Cell Stress Chaperones. 2021;26(2):387-401. PubMed PMID: 33405053.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-κB/NLRP3 axis. AU - Du,Donghua, AU - Lv,Wenting, AU - Su,Rina, AU - Yu,Chunwei, AU - Jing,Xiaoxia, AU - Bai,Nuwenqimuge, AU - Hasi,Surong, Y1 - 2021/01/06/ PY - 2020/07/15/received PY - 2020/11/27/accepted PY - 2020/11/16/revised PY - 2021/09/01/pmc-release PY - 2021/1/7/pubmed PY - 2021/1/7/medline PY - 2021/1/6/entrez KW - Apoptosis KW - Camel whey protein KW - Heat stress KW - Hepatocyte KW - Oxidative stress SP - 387 EP - 401 JF - Cell stress & chaperones JO - Cell Stress Chaperones VL - 26 IS - 2 N2 - Liver damage is the most severe complication of heat stress (HS). Hydrolyzed camel whey protein (CWP) possesses bioactive peptides with obviously antioxidant and anti-inflammatory activities. The current study aims to investigate whether CWP that is hydrolyzed by a simulated gastrointestinal digestion process, named S-CWP, protects BRL-3A hepatocytes from HS-induced damage via antioxidant and anti-inflammatory mechanisms. BRL-3A cells were pretreated with S-CWP before being treated at 43 °C for 1 h, and the levels of the cellular oxidative stress, inflammation, apoptosis, biomarkers for liver function, the activities of several antioxidant enzymes, and the cell viability were analyzed. The expression level of pivotal proteins in correlative signaling pathways was evaluated by western blotting. We confirmed that S-CWP alleviated HS-induced hepatocytes oxidative stress by decreased reactive oxygen species (ROS), nitric oxide (NO), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), protein carbonylation (PCO), and the activities of NADPH oxidase while enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) activities, and GSH content. S-CWP suppressed HS-induced inflammatory response by reducing the phosphorylation of NF-κB p65, the expression of NLRP3, and caspase-1 and finally alleviated caspase-3-mediated apoptosis. S-CWP also alleviated HS-induced hepatocyte injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and restoring Heat Shock Protein 70 (HSP70) expression. Furthermore, S-CWP treatment significantly enhanced the expression of NF-E2-related nuclear factor erythroid-2 (Nrf2) and HO-1. The antioxidant and anti-inflammatory effects of S-CWP were weakened by ML385, a specific Nrf2 inhibitor. Additionally, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, significantly reversed S-CWP-induced reduction in the phosphorylation of NF-κB p65. Thus, our results revealed that S-CWP protected against HS-induced hepatocytes damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NF-κB/NLRP3 axis. SN - 1466-1268 UR - https://www.unboundmedicine.com/medline/citation/33405053/Hydrolyzed_camel_whey_protein_alleviated_heat_stress_induced_hepatocyte_damage_by_activated_Nrf2/HO_1_signaling_pathway_and_inhibited_NF_κB/NLRP3_axis_ L2 - https://dx.doi.org/10.1007/s12192-020-01184-z DB - PRIME DP - Unbound Medicine ER -
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