Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
Authors: Haizhao Yan
Zhimin Mao
Jian Yao
Yanru Huang
Qiaojing Yan
Jianglin Fan
Jingru Hong
Xiawen Yang
Journal: Redox Biology (2021)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Albumin; Colitis; Hydrogen peroxide; Oxidative stress; Reductively modified albumin
Affiliations: Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan., Divison of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan. Electronic address: .

Abstract:  Albumin (Alb) is the most abundant plasma protein with multiple biological functions, including antioxidative property through its thiol activity. Given that inflammatory bowel disease is associated with a decreased level of Alb and an increased level of Alb oxidation, we asked whether Alb could have a therapeutic effect on colitis. Here we tested this possibility. Bovine serum albumin (BSA) was reductively modified with dithiothreitol (DTT) and administrated via gavage or intraperitoneal injection. Dextran sulfate sodium (DSS)-induced mice colitis was associated with massive oxidative stress, as indicated by the elevated sulfenic acid formation in blood, colon tissues, and feces. Treatment of mice with the reductively modified albumin (r-Alb) attenuated the oxidative stress and reduced local inflammation and tissue injury. These effects of r-Alb were only partially achieved by unmodified Alb and wholly lost after blocking the -SH groups with maleimide. In cultured colon epithelial cells, r-Alb prevented DSS- and H2O2-induced ROS elevation and barrier dysfunction, preceded by inhibition of sulfenic acid formation and P38 activation. Further analysis revealed that Alb was susceptible to H2O2-induced oxidation, and it detoxified H2O2 in a -SH group-dependent way. Moreover, Alb reacted with GSH/GSSG via thiol-disulfide exchange and reciprocally regulated the availability of -SH groups. Collectively, our study shows that r-Alb effectively attenuates DSS colitis via -SH group-mediated antioxidative action. Given that the oxidative stress underlies many life-threatening diseases, r-Alb, functioning as a potent antioxidant, could have a wide range of applications. 

Retracted: No

PubPeer comments:
 Figure six appears to include a repeated image. *** ![file] , 
 Thank you very much for reminding us of the repetition. I take it very seriously. I have contacted the first author and checked the original data and reports. Indeed, it is a mistake during figure preparation. She has used A as a a template for D and forget replacing the image. Surely, I will ask the journal for the correction soon. For your reference, I have the original reports and revised figure attached to this message. Thank you very much for your efforts in making the scientific publication solid and clean. Yours sincerely, Jian![file] ![file] ![file] ,