HSP70 induced by hyperosmotic stress partially protects LLC-PK1 cells against nephrotoxic drugs.
Accumulation of HSP70 is related to the cytoprotection. It was evaluated whether hyperosmotic stress induces HSP70 accumulation in LLC-PK1 cells, and protects cells against toxicity provoked by cisplatin (Cis) and cyclosporine A (CyA). Cells were maintained in isosmotic (Iso) or hyperosmotic (H) culture medium for 24 h and then exposed to Cis or CyA for an additional period of 12 or 24 h (groups H+Cis and H+CyA). The H medium did not induce cell death and increased both HSP70 mRNA and protein levels, suggesting a role in cell adaptation to H condition. H medium produced partial cytoprotection against Cis and CyA compared with control cells. Despite the cytoprotection, there was a reduction in HSP70 mRNA and protein levels in H+Cis group. In contrast, the H+CyA group presented high levels of HSP70 mRNA and protein. The induction of HSP70 by H medium was associated with tolerance of LLC-PK1 cells against Cis and CyA cytotoxicity but this protection was induced by different mechanisms and depended on the characteristics of the drug used.
Leitão
Aurilucia A
AA
Nephrology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brasil.
Leite
Cleber A
CA
Santos
Bento C
BC
Boim
Mirian A
MA
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D016572:Cyclosporine / Q000633:toxicity; D019610:Cytoprotection; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007166:Immunosuppressive Agents / Q000633:toxicity; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D009997:Osmotic Pressure; D012333:RNA, Messenger / Q000096:biosynthesis
D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine; D002945:Cisplatin