Wang Gui-Jun, Guo Lian-Yi, Wang Hong-Xin, Yao Yu-Sheng
The First Affiliated Hospital, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Department of Pharmacology, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Am J Transl Res. 2017 Feb 15;9(2):343-354. eCollection 2017.
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume. We found that the IP3R inhibitor (2-APB) and RyR inhibitor (ryanodine) both had significant suppressive effects on the level of [Ca]i, calcium concentration, cell protein content, cell protein synthesis and cell volume of cardiomyocytes treated with TNF-α (P<0.01). Moreover, their combined effects were significantly enhanced compared with their single effects (P<0.01). However, the inhibitor of the L type Ca channel nifedipine exhibited no significant suppressive effects on the increase in [Ca]i, calcium concentration, cell protein content, cell protein synthesis and cell volume of cardiomyocytes induced by TNF-α (P>0.05). Our results suggest that TNF-α probably induces cardiac myocyte hypertrophy by activating IP3R and RyR calcium channels, which control the release of calcium ions from the sarcoplasmic reticulum (SR) in cardiomyocytes. On the other hand, extracellular calcium influx, which is mainly regulated by the L type Ca channel, may not be involved in cardiac myocyte hypertrophy induced by TNF-α.
为了研究哪些钙通道参与肿瘤坏死因子-α（TNF-α）诱导的心肌细胞肥大，用100μg/L的TNF-α处理培养的心肌细胞。此外，使用了三种不同的钙通道阻滞剂（2-氨基乙氧基二苯硼酸（2-APB）、ryanodine和硝苯地平），并仔细观察了每种钙通道阻滞剂对TNF-α诱导的心肌肥大的影响。测量指标包括胞质钙瞬变（[Ca]i）、单个细胞内的钙水平、细胞蛋白含量、细胞蛋白合成和细胞体积。我们发现，IP3R抑制剂（2-APB）和RyR抑制剂（ryanodine）对用TNF-α处理的心肌细胞的[Ca]i水平、钙浓度、细胞蛋白含量、细胞蛋白合成和细胞体积均有显著的抑制作用（P<0.01）。此外，与它们单独的作用相比，它们的联合作用显著增强（P<0.01）。然而，L型钙通道抑制剂硝苯地平对TNF-α诱导的心肌细胞的[Ca]i增加、钙浓度、细胞蛋白含量、细胞蛋白合成和细胞体积没有显著的抑制作用（P>0.05）。我们的结果表明，TNF-α可能通过激活IP3R和RyR钙通道诱导心肌细胞肥大，这两种钙通道控制心肌细胞肌浆网（SR）中钙离子的释放。另一方面，主要由L型钙通道调节的细胞外钙内流可能不参与TNF-α诱导的心肌细胞肥大。
