Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1016/S0891-5849(01)00761-4
Titel (primär) Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: Role of cGMP and heme oxygenase-1
Autor Polte, T.; Hemmerle, A.; Berndt, G.; Grosser, N.; Abate, A.; Schröder, H.
Quelle Free Radical Biology and Medicine
Erscheinungsjahr 2002
Department IMMU
Band/Volume 32
Heft 1
Seite von 56
Seite bis 63
Sprache 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
dauerhafte UFZ-Verlinkung 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