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Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state

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 hav...

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Autores principales: Yang, Xiawen, Mao, Zhimin, Huang, Yanru, Yan, Haizhao, Yan, Qiaojing, Hong, Jingru, Fan, Jianglin, Yao, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897995/
https://www.ncbi.nlm.nih.gov/pubmed/33601276
http://dx.doi.org/10.1016/j.redox.2021.101881
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author Yang, Xiawen
Mao, Zhimin
Huang, Yanru
Yan, Haizhao
Yan, Qiaojing
Hong, Jingru
Fan, Jianglin
Yao, Jian
author_facet Yang, Xiawen
Mao, Zhimin
Huang, Yanru
Yan, Haizhao
Yan, Qiaojing
Hong, Jingru
Fan, Jianglin
Yao, Jian
author_sort Yang, Xiawen
collection PubMed
description 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 H(2)O(2)-induced ROS elevation and barrier dysfunction, preceded by inhibition of sulfenic acid formation and P38 activation. Further analysis revealed that Alb was susceptible to H(2)O(2)-induced oxidation, and it detoxified H(2)O(2) 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.
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spelling pubmed-78979952021-03-03 Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state Yang, Xiawen Mao, Zhimin Huang, Yanru Yan, Haizhao Yan, Qiaojing Hong, Jingru Fan, Jianglin Yao, Jian Redox Biol Research Paper 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 H(2)O(2)-induced ROS elevation and barrier dysfunction, preceded by inhibition of sulfenic acid formation and P38 activation. Further analysis revealed that Alb was susceptible to H(2)O(2)-induced oxidation, and it detoxified H(2)O(2) 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. Elsevier 2021-02-05 /pmc/articles/PMC7897995/ /pubmed/33601276 http://dx.doi.org/10.1016/j.redox.2021.101881 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Yang, Xiawen
Mao, Zhimin
Huang, Yanru
Yan, Haizhao
Yan, Qiaojing
Hong, Jingru
Fan, Jianglin
Yao, Jian
Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title_full Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title_fullStr Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title_full_unstemmed Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title_short Reductively modified albumin attenuates DSS-Induced mouse colitis through rebalancing systemic redox state
title_sort reductively modified albumin attenuates dss-induced mouse colitis through rebalancing systemic redox state
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897995/
https://www.ncbi.nlm.nih.gov/pubmed/33601276
http://dx.doi.org/10.1016/j.redox.2021.101881
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