Morishima Masaki, Fujita Takafumi, Osagawa Satoshi, Kubota Hiroshi, Ono Katsushige
Department of Food and Nutrition, Kindai University Faculty of Agriculture, Nara 631-8505, Japan.
Department of Pathophysiology, Oita University School of Medicine, Oita 879-5593, Japan.
Membranes (Basel). 2021 Jun 25;11(7):470. doi: 10.3390/membranes11070470.
Brain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca channel, Cav3.1 and Cav3.2, in rat neonatal cardiomyocytes exposed to normoxia (21% O) and acute hypoxia (1% O) in vitro for up to 3 h. The exposure of cardiomyocytes to hypoxia (1 h, 3 h) caused a significant upregulation of the mRNAs for hypoxia-inducible factor 1α (), , and , but not tropomyosin-related kinase receptor B (). The upregulation of and caused by hypoxia was completely halted by small interfering RNA (siRNA) targeting (-siRNA) or (-siRNA). Immunocytochemical staining data revealed a distinct upregulation of Cav3.1- and Cav3.2-proteins caused by hypoxia in cardiomyocytes, which was markedly suppressed by -siRNA. These results unveiled a novel regulatory action of BDNF on the T-type Ca channels expression through the HIF-1α-dependent pathway in cardiomyocytes.
脑源性神经营养因子（BDNF）最近被认为是一种心血管调节因子，尤其是在包括冠状动脉疾病、心力衰竭、心肌病和高血压等疾病状态下。在此，我们研究了BDNF对大鼠新生心肌细胞中T型钙通道Cav3.1和Cav3.2的作用，这些细胞在体外分别暴露于常氧（21% O₂）和急性缺氧（1% O₂）环境中长达3小时。将心肌细胞暴露于缺氧环境（1小时、3小时）会导致缺氧诱导因子1α（HIF-1α）、[此处原文缺失部分内容]以及[此处原文缺失部分内容]的mRNA显著上调，但原肌球蛋白相关激酶受体B（TrkB）的mRNA未上调。针对HIF-1α（HIF-1α-siRNA）或[此处原文缺失部分内容]（[此处原文缺失部分内容]-siRNA）的小干扰RNA（siRNA）完全阻止了缺氧引起的[此处原文缺失部分内容]和[此处原文缺失部分内容]的上调。免疫细胞化学染色数据显示，缺氧导致心肌细胞中Cav3.1和Cav3.2蛋白明显上调，而HIF-1α-siRNA显著抑制了这种上调。这些结果揭示了BDNF通过心肌细胞中HIF-1α依赖途径对T型钙通道表达的一种新的调节作用。
