Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes.

Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes.
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C反应蛋白对心肌细胞钠钙交换体1的影响

DOI:
10.3892/etm.2021.10247
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发表时间:
2021-08
影响因子:
2.7
通讯作者:
Chen YX
Chen YX
中科院分区:
医学4区
文献类型:
--
作者:
Xie Y;Li Q;Zhang HF;Huang TC;Yang Y;Lin YQ;Mai JT;Wen ZZ;Yuan WL;Wang JF;Chen YX

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大量研究发现C-反应蛋白(CRP)与心律失常和心脏重构有关。然而,这种关联的潜在机制仍不清楚。钠钙交换器1(sodium-calciumexchanger 1,NCX 1)在细胞内钙离子浓度的调节中起重要作用,与心律失常和心脏重构密切相关。本研究旨在评价CRP对心肌细胞NCX 1和细胞内钙浓度的影响。培养原代新生小鼠心室心肌细胞,并用不同浓度的CRP(0、5、10、20和40 µg/ml)处理。心肌细胞也用NF-κ B特异性抑制剂PTDC和反向NCX 1 KB-R7943的特异性抑制剂处理,然后测量其细胞内钙浓度。采用逆转录-定量PCR和Western blotting检测NCX 1 mRNA和蛋白表达水平,流式细胞仪检测细胞内钙离子浓度。CRP处理显著增加心肌细胞中NCX 1的mRNA和蛋白表达水平(P=0.024),以及细胞内钙浓度(P=0.01)。这些结果被NF-κ B特异性抑制剂PDTC和反向NCX 1的特异性抑制剂KB-R7943显著减弱。CRP通过NF-κB途径显著上调心肌细胞NCX 1表达并增加细胞内钙浓度,表明CRP可能通过直接影响心肌细胞的钙稳态而发挥促心律失常作用。
Numerous previous studies have found that C-reactive protein (CRP) is associated with cardiac arrhythmia and cardiac remodeling. However, the underlying mechanisms of this association remain unclear. Sodium-calcium exchanger 1 (NCX1) serves an important role in the regulation of intracellular calcium concentration, which is closely related with cardiac arrhythmia and cardiac remodeling. The present study aimed to evaluate the effects of CRP on NCX1 and intracellular calcium concentration in cardiomyocytes. Primary neonatal mouse ventricular cardiomyocytes were cultured and treated with varying concentrations of CRP (0, 5, 10, 20 and 40 µg/ml). The cardiomyocytes were also treated with NF-κB-specific inhibitor PTDC and a specific inhibitor of the reverse NCX1 KB-R7943 before their intracellular calcium concentrations were measured. mRNA and protein expression levels of NCX1 were detected by reverse transcription-quantitative PCR and western blotting, respectively and intracellular calcium concentration was evaluated by flow cytometry. CRP treatment significantly increased mRNA and protein expression levels of NCX1 in myocytes (P=0.024), as well as intracellular calcium concentration (P=0.01). These results were significantly attenuated by the NF-κB-specific inhibitor PDTC and a specific inhibitor of the reverse NCX1, KB-R7943. CRP significantly upregulated NCX1 expression and increased intracellular calcium concentration in cardiomyocytes via the NF-κB pathway, suggesting that CRP may serve a pro-arrhythmia role via direct influence on the calcium homeostasis of cardiomyocytes.
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发表时间: 2014-01-01
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