title: SUMOylation occurs in acute kidney injury and plays a cytoprotective role.
abstract: SUMOylation is a form of post-translational modification where small ubiquitin-like modifiers (SUMO) are covalently attached to target proteins to regulate their properties. SUMOylation has been demonstrated during cell stress and implicated in cellular stress response. However, it is largely unclear if SUMOylation contributes to the pathogenesis of kidney diseases, such as acute kidney injury (AKI). Here we have demonstrated a dynamic change of protein SUMOylation in ischemic and cisplatin nephrotoxic AKI in mice. In rat kidney proximal tubular cells (RPTC), cisplatin-induced SUMOylation was diminished by two antioxidants (N-acetylcysteine and dimethylurea), supporting a role of oxidative stress in the activation of SUMOylation. In addition, SUMOylation by SUMO-2/3, but not SUMO-1, was partially suppressed by pifithrin-alpha (a pharmacological inhibitor of p53), supporting a role of p53 in SUMOylation by SUMO-2/3. We further examined the role of SUMOylation during cisplatin treatment of RPTC by using ginkgolic acid (GA), a pharmacological inhibitor of SUMOylation. Pretreatment with GA suppressed SUMOylation and importantly, GA enhanced apoptosis during cisplatin incubation. Taken together, the results demonstrate the first evidence of SUMOylation in AKI and suggest that SUMOylation may play a cytoprotective role in kidney tubular cells.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, United States.
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, United States.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Pharmacology & Toxicology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, United States.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, United States; Charlie Norwood VA Medical Center, Augusta, GA 30912 United States; Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: zdong@gru.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis; D002945:Cisplatin / Q000009:adverse effects / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D025842:SUMO-1 Protein / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D025842:SUMO-1 Protein; D012459:Salicylates; D016159:Tumor Suppressor Protein p53; C112485:ginkgolic acid; D002945:Cisplatin; D000111:Acetylcysteine
keywords: Apoptosis; Cisplatin nephrotoxicity; ROS; Renal ischemia–reperfusion; SUMOylation; p53