Nuclear Membranes ETB Receptors Mediate ET-1-induced Increase of Nuclear Calcium in Human Left Ventricular Endocardial Endothelial Cells
Nuclear Membranes ETB Receptors Mediate ET-1-induced Increase of Nuclear Calcium in Human Left Ventricular Endocardial Endothelial Cells
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DOI：
10.1097/fjc.0000000000000242
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发表时间：
2015-07-01
影响因子：
3
通讯作者：
Jacques, Danielle
中科院分区：
文献类型：
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作者：
Jules, Farah;Avedanian, Levon;Jacques, Danielle
在胎儿人左心室内膜内皮细胞（EECL）中，据报道质膜（PM）ETAR和ETBR均介导ET-1诱导的细胞内钙[Ca]（i）增加;然而，在右EECs（EECR）中，该效应由ETAR介导。在这项研究中，我们验证了是否，作为PM，核膜（NM）ET-1受体激活EECL和EECR诱导核钙（[Ca]（n））的增加，如果这种效果是通过相同的受体类型在PM介导。使用质膜穿孔技术和三维共聚焦显微镜，我们的结果表明，在PM完整细胞，灌流的细胞核的两种类型的细胞与胞质ET-1诱导浓度依赖性的持续增加[Ca]（n）。在EECR中，ETAR拮抗剂阻止ET-1对[Ca]（n）的影响，而不影响EECL。然而，在这两种细胞类型中，胞质ET-1对[Ca]（n）的影响被ETBR拮抗剂阻止。总之，NMs的ETAR和ETBR均介导了胞浆ET-1对EECRs [Ca]（n）的影响。相反，只有NM的ETBR激活介导了EECL中胞质ET-1的作用。因此，介导ET-1对[Ca]（n）影响的NMs受体类型与介导PM对[Ca]（i）升高的NMs受体类型不同。
In fetal human left ventricular endocardial endothelial cells (EECLs), both plasma membrane (PM) ETAR and ETBR were reported to mediate ET-1-induced increase of intracellular calcium [Ca](i); however, this effect was mediated by ETAR in right EECs (EECRs). In this study, we verified whether, as for the PM, nuclear membranes (NMs) ET-1 receptors activation in EECLs and EECRs induce an increase of nuclear calcium ([Ca](n)) and if this effect is mediated through the same receptor type as in PM. Using a plasmalemma-perforated technique and 3D confocal microscopy, our results showed that, as in PM intact cells, superfusion of nuclei of both cell types with cytosolic ET-1 induced a concentration-dependent sustained increase of [Ca](n). In EECRs, the ETAR antagonist prevented the effect of ET-1 on [Ca](n) without affecting EECLs. However, in both cell types, the effect of cytosolic ET-1 on [Ca](n) was prevented by the ETBR antagonist. In conclusion, both NMs' ETAR and ETBR mediated the effect of cytosolic ET-1 on [Ca](n) in EECRs. In contrast, only NMs' ETBR activation mediated the effect of cytosolic ET-1 in EECLs. Hence, the type of NMs' receptors mediating the effect of ET-1 on [Ca](n) are different from those of PM mediating the increase in [Ca](i).