1. Academic Validation
  2. GPA Peptide-Induced Nur77 Localization at Mitochondria Inhibits Inflammation and Oxidative Stress through Activating Autophagy in the Intestine

GPA Peptide-Induced Nur77 Localization at Mitochondria Inhibits Inflammation and Oxidative Stress through Activating Autophagy in the Intestine

  • Oxid Med Cell Longev. 2020 Aug 20;2020:4964202. doi: 10.1155/2020/4964202.
Zhao Deng 1 Qi Liu 1 Miaomiao Wang 1 Hong-Kui Wei 1 2 Jian Peng 1 2
Affiliations

Affiliations

  • 1 Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, 430070 Wuhan, China.
  • 2 The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070 Hubei, China.
Abstract

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. Nur77, belongs to the NR4A subfamily of nuclear hormone receptors, plays a critical role in controlling the pathology of colitis. The aim of this study is to investigate the protection effect and mechanism of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate, in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and intestinal epithelial cells (IECs) stimulated by lipopolysaccharide (LPS). In vivo, GPA treatment alleviates DSS-induced weight loss, disease activity index (DAI) increase, colon length shortening, and colonic pathological damage. Production of proinflammatory cytokines, ROS, and MDA is significantly decreased by GPA treatment. In vitro, GPA significantly inhibits proinflammatory cytokine production, cytotoxicity, ROS, and MDA in IECs. Furthermore, GPA induces Autophagy to suppress inflammation and oxidative stress. GPA promotes Nur77 translocation from the nucleus to mitochondria where it facilitates Nur77 interaction with TRAF6 and p62, leading to the induction of Autophagy. In addition, GPA contributed to the maintenance of tight junction architecture in vivo and in vitro. Taken together, GPA, as a Nur77 modulator, could exert anti-inflammatory and antioxidant effects by inducing Autophagy in IECs, suggesting that GPA may be promising for the prevention of colitis.

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