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 language | English |
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Pages (from-to) | 3660-3671 |
Number of pages | 12 |
Journal | Journal of Cellular Physiology |
Volume | 233 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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