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 language | English (US) |
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Pages (from-to) | 56-63 |
Number of pages | 8 |
Journal | Free Radical Biology and Medicine |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - 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