Oxidative stress response in iron-induced acute nephrotoxicity: enhanced expression of heat shock protein 90.
Iron overload with ferric nitrilotriacetate (Fe-NTA) induces acute renal proximal tubular necrosis, a consequence of oxidative tissue damage, that leads to a high incidence of renal adenocarcinoma in rodents. In the present study, we determined the proteins preferentially produced in response to the Fe-NTA-induced oxidative injury. A single intraperitoneal Fe-NTA treatment led to the enhanced production of a number of proteins with molecular masses of 85-95 kDa. These included heat shock protein 90 (HSP90) as determined by immunoprecipitation. The enhanced production of HSP90 was prominent in the renal tubular cells. Steady accumulation of HSP90 was observed in the subacute toxicity experiments with multiple injections of Fe-NTA, suggesting that the enhanced production of HSP90 is important in increasing resistance to subsequent injury caused by the Fe-NTA-induced oxidative stress.
Fukuda
A
A
Laboratory of Food and Biodynamics, Nagoya University School of Agriculture, Japan.
Osawa
T
T
Oda
H
H
Tanaka
T
T
Toyokuni
S
S
Uchida
K
K
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002273:Carcinogens; D005290:Ferric Compounds; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D007501:Iron; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate