Abstract |
Preconditioning in cultured cardiomyocytes elevates the expression of several protective genes including Glut-4 and heat shock protein (HSP)70. Hypoxia-inducible factor-1 (HIF-1) is known to mediate the transcriptional activation of hypoxia-responsive genes. In this study, we examined the effect of adenovirus-mediated expression of constitutively stable hybrid forms of HIF-1alpha on cardiomyocyte viability and gene expression. Cultured neonatal rat cardiomyocytes were subjected to simulated ischemia-reperfusion with or without preinfection with recombinant adenoviral vectors [Ad2/HIF-1alpha/ herpes simplex virus protein VP16 and Ad2/HIF-1alpha/ nuclear factor-kappaB ( NF-kappaB)]. Cellular viability and mRNA levels of several cardioprotective genes were measured. We demonstrated that infection with Ad2/HIF-1alpha/ VP16 and Ad2/HIF-1alpha/ NF-kappaB mimicked the upregulation of the mRNA levels of vascular endothelial growth factor ( VEGF), Glut-1, Glut-4, HSP70, and inducible NO synthase (iNOS) and the protection of cultured neonatal rat cardiomyocytes by late-phase preconditioning against simulated ischemia-reperfusion. The same dose of a control viral vector expressing no transgene had no effect. Preconditioning also elevated HIF-1alpha protein levels. These results suggest that adenovirus-mediated expression of HIF-1alpha/ VP16 or HIF-1alpha/ NF-kappaB, a constitutively stable hybrid transcriptional factor, protected cultured neonatal cardiomyocytes against simulated ischemia-reperfusion injury by inducing multiple protective genes.
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Authors | Taro Date, Seibu Mochizuki, Adam J Belanger, Midori Yamakawa, Zhengyu Luo, Karen A Vincent, Seng H Cheng, Richard J Gregory, Canwen Jiang |
Journal | American journal of physiology. Cell physiology
(Am J Physiol Cell Physiol)
Vol. 288
Issue 2
Pg. C314-20
(Feb 2005)
ISSN: 0363-6143 [Print] United States |
PMID | 15496478
(Publication Type: Journal Article)
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Chemical References |
- DNA-Binding Proteins
- Herpes Simplex Virus Protein Vmw65
- Hif1a protein, rat
- Hypoxia-Inducible Factor 1
- Hypoxia-Inducible Factor 1, alpha Subunit
- NF-kappa B
- Nuclear Proteins
- RNA, Messenger
- Transcription Factors
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Topics |
- Adenoviridae
- Animals
- Cell Survival
(drug effects)
- Cells, Cultured
- DNA-Binding Proteins
(biosynthesis, genetics)
- Gene Expression Regulation
(drug effects, physiology)
- Genetic Vectors
- Herpes Simplex Virus Protein Vmw65
(biosynthesis, genetics)
- Hypoxia-Inducible Factor 1
- Hypoxia-Inducible Factor 1, alpha Subunit
- Ischemic Preconditioning, Myocardial
- Myocytes, Cardiac
(drug effects, metabolism)
- NF-kappa B
(biosynthesis, genetics)
- Nuclear Proteins
(biosynthesis, genetics)
- RNA, Messenger
(analysis)
- Rats
- Reperfusion Injury
(physiopathology)
- Transcription Factors
(biosynthesis, genetics)
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