HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Expression of constitutively stable hybrid hypoxia-inducible factor-1alpha protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury.

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.
AuthorsTaro Date, Seibu Mochizuki, Adam J Belanger, Midori Yamakawa, Zhengyu Luo, Karen A Vincent, Seng H Cheng, Richard J Gregory, Canwen Jiang
JournalAmerican 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
PMID15496478 (Publication Type: Journal Article)
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
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: