NEFAs activate the oxidative stress-mediated NF-κB signaling pathway to induce inflammatory response in calf hepatocytes. Issue 145 (January 2015)

• Record Type: Journal Article
• Authors: Shi, Xiaoxia; Li, Dangdang; Deng, Qinghua; Li, Yu; Sun, Guoquan; Yuan, Xue; Song, Yuxiang; Wang, Zhe; Li, Xiaobing; Li, Xinwei; Liu, Guowen
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 145(2015)
• Page Start: 103
• Page End: 112
• Publication Date: 2015-01
• Subjects: NEFAs nonesterified fatty acids -- PDTC pyrrolidine dithiocarbamate -- NAC N-acetylcysteine -- NEB negative energy balance -- ROS reactive oxygen species -- MDA malonaldehyde -- GSH-Px glutathione peroxidase -- SOD superoxide dismutase -- CAT catalase -- SFA saturated fatty acids -- PUFAs polyunsaturated fatty acids -- ROM reactive oxygen metabolites -- TBARS thiobarbituric acid reactive substances -- FFAs free fatty acids; Non-esterified fatty acids -- Cow ketosis -- Oxidative stress -- Inflammatory injury -- Bovine hepatocytes; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.10.014
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: NEFAs treatment induced oxidative stress in bovine hepatocytes. NEFAs treatment activated NF-κB pathway in bovine hepatocytes. NEFAs triggered inflammatory response through NF-κB pathway in bovine hepatocytes. We partly explained the inflammatory mechanism in dairy cows with ketosis. Abstract: Non-esterified fatty acids (NEFAs) are important induction factors of inflammatory responses in some metabolic diseases. High plasma levels of NEFAs and oxidative stress exist in the dairy cows with ketosis. The aim of this study was to investigate whether high levels of NEFAs can induce inflammatory response and the specific molecular mechanism in the hepatocytes of dairy cow. In vitro, primary cultured bovine hepatocytes were treated with different concentrations of NEFAs, PDTC (an NF-κB inhibitor) and NAC (an antioxidant). NEFAs significantly activated NF-κB pathway. Activated NF-κB upregulated the release of pro-inflammatory cytokines, thereby inducing inflammatory response in bovine hepatocytes. When PDTC was added, activation of NF-κB-mediated inflammatory response induced by NEFAs was inhibited. NEFAs treatment results in the overproduction of the markers of oxidative stress, reactive oxygen species (ROS) and malondialdehyde (MDA), which were ameliorated by NAC treatment. These increased ROS and MDA were caused by decreasing activity of antioxidant system, including glutathione peroxidase, superoxide dismutase and catalase, in bovine hepatocytes treated with NEFAs. NAC also ameliorated NEFAs-mediated NF-κB activation and the release of pro-inflammatory cytokines. These results indicate that high concentrations of NEFAs can induce cattle hepatocytes inflammatory response through activating the oxidative stress-mediated NF-κB signaling pathway.