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Erschienen in: Cardiovascular Toxicology 2/2012

01.06.2012

NAD(P)H: Quinone Oxidoreductase 1 is Induced by Progesterone in Cardiomyocytes

verfasst von: Stephen Morrissy, Joshua Strom, Sally Purdom-Dickinson, Qin M. Chen

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2012

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Abstract

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that catalyzes two-electron reduction of various quinones by utilizing NAD(P)H as an electron donor. Our previous study found that progesterone (PG) can protect cardiomyocytes from apoptosis induced by doxorubicin (Dox). Microarray analyses of genes induced by PG had led to the discovery of induction of NQO1 mRNA. We report here that PG induces NQO1 protein and its activity in a dose-dependent manner. Whereas NQO1 is well known as a target gene of Nrf2 transcription factor due to the presence of antioxidant response element (ARE) in the promoter, PG did not activate the ARE, suggesting Nrf2-independent induction of NQO1. To address the role of NQO1 induction in PG-induced cytoprotection, we tested the effect of NQO1 inducer β-naphthoflavone and inhibitor dicoumarol. Induction of NQO1 by β-naphthoflavone decreased Dox-induced apoptosis and potentiated the protective effect of PG as measured by caspase-3 activity. PG-induced NQO1 activity was inhibited with dicoumarol, which did not affect PG-induced cytoprotection. Dicoumarol treatment alone potentiated Dox-induced caspase-3 activity. These data suggest that while NQO1 plays a role in PG-induced cytoprotection, there are additional components contributing to PG-induced cytoprotection.
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Metadaten
Titel
NAD(P)H: Quinone Oxidoreductase 1 is Induced by Progesterone in Cardiomyocytes
verfasst von
Stephen Morrissy
Joshua Strom
Sally Purdom-Dickinson
Qin M. Chen
Publikationsdatum
01.06.2012
Verlag
Humana Press Inc
Erschienen in
Cardiovascular Toxicology / Ausgabe 2/2012
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-011-9144-9

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