Synergistic effect of HIF-1α and FoxO3a trigger cardiomyocyte apoptosis under hyperglycemic ischemia condition

Ya Fang Chen, Sudhir Pandey, Cecilia Hsuan Day, Yu Feng Chen, Ai Zhi Jiang, Tsung Jung Ho, Ray Jade Chen, Vijaya V. Padma, Wei Wen Kuo, Chih Yang Huang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1α and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1α and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death. Our results highlighted the importance of the synergistic role of HIF-1α and FoxO3a in cardiomyocyte death which may add insight into therapeutic approaches to pathophysiology associated with ischemic diabetic cardiomyopathies.

Original languageEnglish
Pages (from-to)3660-3671
JournalJournal of Cellular Physiology
Volume233
Issue number4
DOIs
Publication statusPublished - Apr 2018

Keywords

  • BCL2/Adenovirus E1B Nineteen kilo Dalton Interacting Protein 3 (BNIP3)
  • Diabetic hyperglycemic
  • Forkhead box O3 (FoxO3)
  • Hyperglycemia
  • Hypoxia-inducible factor-1 alpha (HIF-1α)
  • Ischemia hypoxia

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Chen, Y. F., Pandey, S., Day, C. H., Chen, Y. F., Jiang, A. Z., Ho, T. J., Chen, R. J., Padma, V. V., Kuo, W. W., & Huang, C. Y. (2018). Synergistic effect of HIF-1α and FoxO3a trigger cardiomyocyte apoptosis under hyperglycemic ischemia condition. Journal of Cellular Physiology, 233(4), 3660-3671. https://doi.org/10.1002/jcp.26235