title: Early response as shown by enhancement of transglutaminase 1 expression after cisplatin-induced acute kidney injury.
abstract: Acute kidney injury (AKI) is caused by drugs and other stimuli, which limits the use of several therapeutic approaches. The AKI mouse model generated by intraperitoneal administration with cisplatin, one of the most widely used anti-cancer drugs, is generally applied to study on this disease. Transglutaminases are posttranslational modifying enzymes that catalyze irreversible cross-linking reactions between proteins in several biological events such as skin formation and blood coagulation. In this study, we found an increase in the expression level of transglutaminase (TG1) in the kidney of mice which had been injected with cisplatin and underwent progressive nephrotoxicity. Before the appearance of the tentative symptoms of renal failure, which is apparent by morphological damage in the kidney and increases in blood creatinine levels, both the expression level and activity of TG1 rapidly increased mainly at the proximal tubule. On the other hand, the protein expression level of another major isozyme (TG2) remained mostly unaltered. This investigation will provide a possible basal-level biomarker and also information on progression of renal failure from the aspect of the protein-modifying enzyme, transglutaminase.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Yamane
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tatsukawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan. Electronic address: hitomi@ps.nagoya-u.ac.jp.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Hitomi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000201:enzymology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000652:urine; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000378:metabolism* / Q000652:urine
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D003404:Creatinine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; C105804:transglutaminase 1; D019204:GTP-Binding Proteins; D002945:Cisplatin
keywords: Cisplatin; Kidney; Renal failure; Transglutaminase