Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation.

Alexander G. Minchenko, Martin J. Stevens, Lauren White, Omorodola I. Abatan, Katalin Komjáti, Pal Pacher, Csaba Szabó, Irina G. Obrosova

    Research output: Contribution to journalArticlepeer-review

    85 Scopus citations

    Abstract

    We hypothesize that poly (ADP-ribosyl)ation, that is, poly (ADP-ribose) polymerase (PARP)-dependent transfer of ADP-ribose moieties from NAD to nuclear proteins, plays a role in diabetic nephropathy. We evaluated whether PARP activation is present and whether two unrelated PARP inhibitors, 3-aminobenzamide (ABA) and 1,5-isoquinolinediol (ISO), counteract overexpression of endothelin-1 (ET-1) and ET receptors in the renal cortex in short-term diabetes. The studies were performed in control rats and streptozotocin-diabetic rats treated with/without ABA or ISO (30 and 3 mg x kg(-1) x day(-1), intraperitoneally, for 2 weeks after 2 weeks of diabetes). Poly (ADP-ribose) immunoreactivity was increased in tubuli, but not glomeruli, of diabetic rats and this increase was corrected by ISO, whereas ABA had a weaker effect. ET-1 concentration (ELISA) was increased in diabetic rats, and this elevation was blunted by ISO. ET-1, ET(A), and ET(B) mRNA (ribonuclease protection assay), but not ET-3 mRNA (RT/PCR), abundance was increased in diabetic rats, and three variables were, at least, partially corrected by ISO. ABA produced a trend towards normalization of ET-1 concentration and ET-1, ET(A), and ET(B) mRNA abundance, but the differences with untreated diabetic group were not significant. Poly(ADP-ribosyl)ation is involved in diabetes-induced renal overexpression of ET-1 and ET receptors. PARP inhibitors could provide a novel therapeutic approach for diabetic complications including nephropathy, and other diseases that involve the endothelin system.

    Original languageEnglish (US)
    Pages (from-to)1514-1516
    Number of pages3
    JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
    Volume17
    Issue number11
    DOIs
    StatePublished - Aug 2003

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

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