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Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells.

Authors: Liu, Y  Huo, Z  Yan, B  Lin, X  Zhou, ZN  Liang, X  Zhu, W  Liang, D  Li, L  Liu, Y  Zhao, H  Sun, Y  Chen, YH 
Citation: Liu Y, etal., Biochem Biophys Res Commun. 2010 Oct 15;401(2):231-7. doi: 10.1016/j.bbrc.2010.09.037. Epub 2010 Sep 16.
Pubmed: (View Article at PubMed) PMID:20849813
DOI: Full-text: DOI:10.1016/j.bbrc.2010.09.037

Prolyl hydroxylases (PHDs) are dioxygenases that use oxygen as a co-substrate to hydroxylate proline residues. Three PHD isoforms (PHD1, PHD2 and PHD3) have been identified in mammalian cells. PHD3 expression is upregulated in some cardiac diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury and congestive heart failure, all of which are associated with apoptosis. However, the role of PHDs in cardiomyocyte apoptosis remains unknown. Here, we have found that exposure of embryonic rat heart-derived H9c2 cells to doxorubicin (DOX) induced cell apoptosis as evaluated by caspase-3/7 activity, mitochondrial membrane potential (Deltapsim) and cell viability, and that this apoptosis was linked to PHD3 upregulation. PHD inhibition or PHD3 silencing substantially ameliorated DOX-induced apoptosis, but PHD1 or PHD2 knockdown did not significantly influence apoptosis. Furthermore, immunoprecipitation experiments showed that PHD3 upregulation reduced the formation of the Bax-Bcl-2 complex, inhibiting the anti-apoptotic effect of Bcl-2. Thus, PHD3 upregulation may be partially responsible for DOX-induced cardiomyocyte apoptosis via its interaction with Bcl-2. Inhibition of PHD3 is likely to be cardioprotective against apoptosis in some heart disorders.


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CRRD Object Information
CRRD ID: 8553662
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
Status: ACTIVE


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