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 Szabo, Irina G. Obrosova

Research output: Contribution to journalArticle

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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
StatePublished - 2003
Externally publishedYes

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Endothelin A Receptors
Endothelin Receptors
Poly(ADP-ribose) Polymerases
Endothelin-1
Medical problems
Rats
Chemical activation
Kidney
Adenosine Diphosphate
Messenger RNA
Adenosine Diphosphate Ribose
Poly Adenosine Diphosphate Ribose
Rat control
Endothelins
Diabetic Nephropathies
Diabetes Complications
Streptozocin
Nuclear Proteins
NAD
Ribonucleases

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Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation. / Minchenko, Alexander G.; Stevens, Martin J.; White, Lauren; Abatan, Omorodola I.; Komjáti, Katalin; Pacher, Pal; Szabo, Csaba; Obrosova, Irina G.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 17, No. 11, 2003, p. 1514-1516.

Research output: Contribution to journalArticle

Minchenko, Alexander G. ; Stevens, Martin J. ; White, Lauren ; Abatan, Omorodola I. ; Komjáti, Katalin ; Pacher, Pal ; Szabo, Csaba ; Obrosova, Irina G. / Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2003 ; Vol. 17, No. 11. pp. 1514-1516.
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T1 - Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation.

AU - Minchenko, Alexander G.

AU - Stevens, Martin J.

AU - White, Lauren

AU - Abatan, Omorodola I.

AU - Komjáti, Katalin

AU - Pacher, Pal

AU - Szabo, Csaba

AU - Obrosova, Irina G.

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AB - 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.

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