title: Redox regulation of actin by thioredoxin-1 is mediated by the interaction of the proteins via cysteine 62.
abstract: Actin is a highly conserved protein in eukaryotic cells, and has been identified as one of the main redox targets by redox proteomics under oxidative stress. However, little is known about the mechanisms of regulation of the redox state of actin. In this study, we investigated how thioredoxin-1 (Trx1) affected the redox state of actin and its polymerization under oxidative stress in SH-SY5Y cells. Trx1 decreased the levels of reactive oxygen species (ROS) in the cells, and cysteine residues at positions 32, 35, and 69 of the Trx1 protein were active sites for redox regulation. Actin could be kept in a reduced state by Trx1 under H(2)O(2) stimulation. A physical interaction was found to exist between actin and Trx1. Cysteine 62 in Trx1 was the key site that interacted with actin, and it was required to maintain cellular viability and anti-apoptotic function. Taken together, these results suggested that Trx1 could protect cells from apoptosis under oxidative stress not only by increasing the total antioxidant capability and decreasing the ROS levels, but also by stabilizing the actin cytoskeletal system, which cooperatively contributed to the enhancement of cell viability and worked against apoptosis.
authors.affiliation: Department of Cellular and Molecular Biology, State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wang
authors.forename: Shukuan
authors.initials: S
authors.lastname: Ling
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Zhao
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Jielin
authors.initials: J
authors.lastname: Nie
authors.forename: Lina
authors.initials: L
authors.lastname: Qu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Shen
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Bai
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Li
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism*; D019943:Amino Acid Substitution / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D019163:Reducing Agents / Q000494:pharmacology; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics; D013879:Thioredoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000199:Actins; D000975:Antioxidants; D017382:Reactive Oxygen Species; D019163:Reducing Agents; C491203:TXN protein, human; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase; D003545:Cysteine