Publication Details |
Category | Text Publication |
Reference Category | Journals |
DOI | 10.1016/S0891-5849(01)00761-4 |
Title (Primary) | Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: Role of cGMP and heme oxygenase-1 |
Author | Polte, T.; Hemmerle, A.; Berndt, G.; Grosser, N.; Abate, A.; Schröder, H. |
Source Titel | Free Radical Biology and Medicine |
Year | 2002 |
Department | IMMU |
Volume | 32 |
Issue | 1 |
Page From | 56 |
Page To | 63 |
Language | englisch |
Keywords | Immunosuppression; Guanylyl cyclase; Antioxidant; Bilirubin; LLC-PK1 cells; Free radicals |
Abstract | Using cultured proximal renal tubular epithelial cells (LLC-PK1), the present study investigates the effect of atrial natriuretic peptide (ANP) on cytotoxicity induced by cyclosporin A (CsA). Preincubation with ANP (1-100 nM) protected LLC-PK1 cells from CsA-induced toxicity in a concentration-dependent manner. A cytoprotective effect comparable to ANP was observed when preincubating the cells with 8-bromo cGMP (1-100 muM) or the antioxidant heme oxygenase (HO) metabolite bilirubin (0.1-10 muM). ANP or cGMP produced increases in HO-1 protein levels at concentrations that were also effective in cellular protection. Moreover, incubation with ANP or 8-bromo cGMP led to increased HO activity, i.e., formation of bilirubin in the cell lysate (up to 3-fold over basal). Tin protoporphyrin-IX (SnPP; 19 muM), an inhibitor of HO activity, completely abolished ANP-induced cytoprotection. Our results demonstrate that HO-1 is a cellular target of ANP and cGMP in renal cells. HO-1 induction and ensuing formation of antioxidant metabolites may be a novel pathway by which ANP protects from CsA-dependent nephrotoxicity and preserves renal function. (C) 2001 Elsevier Science Inc |
Persistent UFZ Identifier | https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=5897 |
Polte, T., Hemmerle, A., Berndt, G., Grosser, N., Abate, A., Schröder, H. (2002): Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: Role of cGMP and heme oxygenase-1 Free Radic. Biol. Med. 32 (1), 56 - 63 10.1016/S0891-5849(01)00761-4 |