The effect of hypoxia-inducible factor 1-alpha on hypoxia-induced apoptosis in primary neonatal rat ventricular myocytes.
OBJECTIVE
To study the role of hypoxia-inducible factor 1-alpha (HIF-1alpha) on hypoxia-induced apoptosis in primary neonatal rat ventricular myocytes.


METHODS
Primary neonatal rat ventricular myocytes were exposed to hypoxia for 24 hours. HIF-1alpha activity was suppressed by treating the cells with 3-(5'-hydroxymethyl-2'- furyl)-1-benzyl indazole (YC-1). The degree of cell apoptosis was assessed by Hoechst 33258 DNA staining. The levels of HIF-1alpha and the pro-apoptotic proteins Bnip3, Bax and Bad were measured with western blotting.


RESULTS
On exposure to hypoxia, there was an increase in the expression levels of HIF-1alpha, and the pro-apoptotic protein Bnip3 was upregulated. Suppression of HIF-1alpha activity by YC-1 treatment was followed by blockade of hypoxia-induced apoptosis and Bnip3 expression; however, the changes in the levels of Bax and Bad expression were unclear.


CONCLUSIONS
Acute hypoxia enhanced primary neonatal rat ventricular myocyte apoptosis through the activation of HIF-1alpha and a mechanism that perhaps involved Bnip3. Targeting HIF-1alpha may be a new strategy for reducing the degree of hypoxia-induced apoptosis in ventricular myocytes.
Zhou
Yan-Fang
YF
Department of Cardiology, First Affiliated Hospital of China Medical University, Shenyang, China.
Zheng
Xiao-Wei
XW
Zhang
Guo-Hui
GH
Zong
Zhi-Hong
ZH
Qi
Guo-Xian
GX
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism
C505650:BNIP3 protein, rat; C494821:Bad protein, rat; C494828:Bax protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D010100:Oxygen