Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Department of Obstetrics and Gynecology, Taichung Veteran's General Hospital, Taichung, Taiwan.
J Cell Physiol. 2018 Apr;233(4):3660-3671. doi: 10.1002/jcp.26235. Epub 2017 Nov 16.
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.
心肌细胞死亡是缺血和心力衰竭的一个重要发病特征。通过这项研究，我们展示了 HIF-1α 和 FoxO3a 在缺氧合并高糖水平下的心肌细胞凋亡中的协同作用。使用基因特异性小干扰 RNA（siRNA）、半定量逆转录聚合酶链反应（RT-PCR）、Western blot、免疫荧光、核质定位和 TUNEL 检测技术，我们确定在高糖合并缺氧条件下，HIF-1α 和 FoxO3a 的联合功能导致 BNIP3 的表达增强，从而诱导心肌细胞死亡。我们的结果强调了 HIF-1α 和 FoxO3a 在心肌细胞死亡中的协同作用的重要性，这可能为与缺血性糖尿病心肌病相关的病理生理学治疗方法提供新的思路。
