Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis
Activation of calcium-sensing receptor increases TRPC3/6 expression in T lymphocyte in sepsis
复制标题
脓毒症中钙敏感受体的激活增加T淋巴细胞中TRPC3/6的表达
DOI：
10.1016/j.molimm.2014.10.018
复制
发表时间：
2015-03-01
影响因子：
3.6
通讯作者：
Sun, Yi-hua
中科院分区：
文献类型：
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作者：
Wu, Qiu-yue;Sun, Ming-rui;Sun, Yi-hua
脓毒症是由感染引起的全身炎症反应综合征。 T淋巴细胞在这种疾病中发挥着重要作用。瞬时受体电位 (TRP) 通道和钙敏感受体 (CaSR) 在淋巴细胞中表达，促进细胞内 Ca2+ 释放。然而，关于脓毒症 T 淋巴细胞中 CaSR 和 TRP 通道之间联系的数据很少。本研究通过Ca2+成像和Western blotting，我们发现脓毒症大鼠外周血T淋巴细胞中TRPC3和TRPC6蛋白表达较高。 SR/ER Ca2+ ATPase 抑制剂毒胡萝卜素 (TG) 和 CaSR 激动剂 NPS R-568 也增加了 TRPC3 和 TRPC6 蛋白的表达，而 PLC-IP3 通道阻断剂 U73122 和 TRPC 通道抑制剂 SKF96365 可逆转这一现象。通过 Ca2+ 成像，我们发现 TG 消耗内质网 Ca2+ 储备会引起细胞质 Ca2+ 短暂升高，然后根据细胞外 Ca2+ 持续增加。但是，SKF96365，而不是维拉帕米（L 型通道抑制剂）和 NiCl2（Na+/Ca2+ 交换抑制剂），抑制了相对较高的 [Ca2+](i)。 NPS R-568也产生了相同的效果，并且[Ca2+]的持续时间； U73122 完全消除了增加，并且在 [Ca2+](o) 不存在的情况下减少了。 NPS R-568 和 TG 增加了脓毒症 T 淋巴细胞的凋亡率，而 SKF96365 和 U73122 可以抑制这种凋亡率。这些结果表明脓毒症中CaSR激活促进TRPC3和TRPC6的表达，并通过PLC-IP3信号通路增强T淋巴细胞凋亡。 (C) 2014 Elsevier Ltd. 保留所有权利。
Sepsis is a systemic inflammatory response syndrome induced by infection. T Lymphocytes play an important role in this disease. Transient receptor potential (TRP) channels and calcium-sensing receptors (CaSR) are expressed in lymphocytes to promote intracellular Ca2+ release. However, data about the link between CaSR and TRP channels in septic T lymphocytes are few. In this study, by Ca2+ imaging and Western blotting, we found that in septic rat peripheral blood T lymphocytes expressions of TRPC3 and TRPC6 proteins are higher. The SR/ER Ca2+ ATPase inhibitor thapsigargin (TG) and CaSR agonist NPS R-568 also increased expressions of TRPC3 and TRPC6 proteins, which were reversed by PLC-IP3 channel blocker U73122 and TRPC channels inhibitor SKF96365. By Ca2+ imaging, we found that the depletion of ER Ca2+ stores by TG elicited a transient rise in cytoplasmic Ca2+, followed by sustained increase depending on extracellular Ca2+. But, SKF96365, not Verapamil (L-type channels inhibitor) and NiCl2 (Na+/Ca2+ exchanger inhibitor), inhibited the relatively high [Ca2+](i). NPS R-568 also resulted in the same effect, and the duration of [Ca2+]; increase was eliminated completely by U73122 and was reduced in the absence of [Ca2+](o). NPS R-568 and TG increased the apoptotic ratio of septic T lymphocytes, which can be suppressed by SKF96365 and U73122. These results suggested that CaSR activation promoted the expression of TRPC3 and TRPC6 and enhanced T lymphocytes apoptosis through PLC-IP3 signaling pathway in sepsis. (C) 2014 Elsevier Ltd. All rights reserved.