Atrial natriuretic peptide reduces cyclosporin toxicity in renal cells: Role of cGMP and heme oxygenase-1

Tobias Polte, Anke Hemmerle, Georg Berndt, Nina Grosser, Aida Abate, Henning Schröder

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 μM) or the antioxidant heme oxygenase (HO) metabolite bilirubin (0.1-10 μM). 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 μM), 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.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalFree Radical Biology and Medicine
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2002

Bibliographical note

Funding Information:
This work was supported by the Deutsche Forschungsgemeinschaft (Schr 298/8-3 and PO 731/1-1).

Keywords

  • Antioxidant
  • Bilirubin
  • Free radicals
  • Guanylyl cyclase
  • Immunosuppression
  • LLC-PK1 cells

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