title: A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure.
abstract: Previous studies from our laboratory showed that increased fatty acid oxidation by the kidney is cytoprotective during cisplatin (CP)-mediated nephrotoxicity. In this study, we determined the effects of CP and fibrates on peroxisome proliferation and the expression of liver fatty acid-binding protein (L-FABP) in normal mice, and in mice transgenically overexpressing human L-FABP (h-L-FABP). Labeling of peroxisomes demonstrated reduced peroxisomal staining in the proximal tubule of CP-treated mice compared with control mice. There was increased peroxisomal labeling in the proximal tubules of both control and CP-treated mice when either was treated with fibrate; a known peroxisome proliferator-activated receptor-alpha ligand. L-FABP protein expression, not detected in control or CP-treated mice, was significantly increased in the proximal tubules of fibrate-treated mice of either group. In the transgenic mice, CP increased the shedding of h-L-FABP in the urine, which was decreased by fibrate as was the acute renal failure. A cytosolic pattern of h-L-FABP expression was found in the proximal tubules of untreated transgenic mice with a nuclear presence in CP-treated mice. Fibrate pretreatment restored the cytosolic expression pattern in CP-treated mice. Our study shows that fibrate may improve CP-induced acute renal failure due to both peroxisome proliferation and increased L-FABP in the cytosol of the proximal tubule.
authors.affiliation: Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Negishi
authors.forename: E
authors.initials: E
authors.lastname: Noiri
authors.forename: T
authors.initials: T
authors.lastname: Sugaya
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Megyesi
authors.forename: K
authors.initials: K
authors.lastname: Nagothu
authors.forename: D
authors.initials: D
authors.lastname: Portilla
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D020675:Peroxisomes / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C493319:FABP1 protein, human; C493320:Fabp1 protein, mouse; D050556:Fatty Acid-Binding Proteins; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; C006253:pirinixic acid; D003404:Creatinine; D002945:Cisplatin