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

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.

• Authors: 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
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 233 Issue 4 Pg. 3660-3671 (04 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 29030976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• BNIP3 protein, rat
• FOXO3 protein, rat
• Forkhead Box Protein O3
• Hypoxia-Inducible Factor 1, alpha Subunit
• Membrane Proteins
• Mitochondrial Proteins
• RNA, Small Interfering

Topics

• Animals
• Apoptosis (physiology)
• Cell Hypoxia (physiology)
• Cells, Cultured
• Forkhead Box Protein O3 (metabolism)
• Hyperglycemia (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Ischemia (metabolism)
• Membrane Proteins (metabolism)
• Mitochondrial Proteins (metabolism)
• Myocytes, Cardiac (metabolism)
• RNA, Small Interfering (metabolism)
• Rats
• Signal Transduction (physiology)