Enzyme engineering (Los Angeles, Calif.)最新文献

筛选

英文中文

Radicalization of Glyceraldehyde-3-Phosphate Dehydrogenase by HOCl in Living Cells. 活细胞中 HOCl 对甘油醛-3-磷酸脱氢酶的辐射作用

Enzyme engineering (Los Angeles, Calif.) Pub Date : 2015-01-01

Sandra E Gomez-Mejiba, Zili Zhai, Marcos D Muñoz, Maria C Della Vedova, Kalina Ranguelova, Michael T Ashby, Dario C Ramirez

{"title":"Radicalization of Glyceraldehyde-3-Phosphate Dehydrogenase by HOCl in Living Cells.","authors":"Sandra E Gomez-Mejiba, Zili Zhai, Marcos D Muñoz, Maria C Della Vedova, Kalina Ranguelova, Michael T Ashby, Dario C Ramirez","doi":"","DOIUrl":"","url":null,"abstract":"A number of post-translational oxidative modifications of the enzyme \"cell-redox sensor\" glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been reported. These modifications affect GAPDH structure, function, and cell fate; however no free-radical mechanisms have been reported in these processes. Herein we used the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-based spin trapping techniques to examine a novel free radical mechanism that causes GAPDH inactivation and aggregation in RAW264.7 cells primed with lipopolysaccharide (LPS). In these primed cells, GAPDH is oxidized by myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) resulting in loss of enzyme activity and aggregation, accumulation of lactate and cell death. Due to the close spatial and physical proximity between MPO and GAPDH, and the oxidizing potential of HOCl, it may be the main species that triggers radicalization of GAPDH that ultimately results in enzyme aggregation and inactivation in LPS-primed macrophages. Lysine residues are the primary radicalization sites formed upon reaction of HOCl with the enzyme. Our data highlight the important relationship between radicalization of GAPDH and fate of stressed cells, which might help teasing out the cell response to stress at sites of inflammation.","PeriodicalId":520257,"journal":{"name":"Enzyme engineering (Los Angeles, Calif.)","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0