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Pannexin 1 plays a pro-survival role by attenuating P2X7 receptor-mediated Ca2+ influx
Cell Calcium ( IF 4.3 ) Pub Date : 2021-08-25 , DOI: 10.1016/j.ceca.2021.102458
Rutambhara Purohit 1 , Amal Kanti Bera 1
Affiliation  

Extracellular ATP works as an autocrine and/or paracrine signaling molecule by activating plasma membrane-localized purinergic receptors. Stimulation of purinergic P2X7 receptor (P2X7R) increases cytosolic Ca2+ ([Ca2+]c), which in turn activates Pannexin 1 (Panx1) channel. In earlier studies, Panx1 and P2X7R have been shown to interact physically. Also, both the channels have been implicated in similar pathophysiological processes. In this study, we investigated the effect of Panx1 on P2X7R-mediated Ca2+influx. Panx1 attenuated P2X7R-mediated [Ca2+]c rise in CHO-K1 and HEK-293 cells. [Ca2+]c rise was higher in Panx1 knockdown astrocytes. The inhibitory effect was unaffected in the presence of Panx1 blocker, carbenoxolone. The region between 350th and 386th amino acid residues in the carboxyl terminus (CT) of Panx1 was found to be crucial for inhibiting P2X7R. Like full-length Panx1, the CT (350th to 426th amino acids) alone was able to attenuate the [Ca2+]c rise. Further, CT prevented cell death caused by P2X7R overactivation. Based on our results, we propose a novel pro-survival role of Panx1 exerted by modulating P2X7R.



中文翻译:

Pannexin 1 通过减弱 P2X7 受体介导的 Ca2+ 流入发挥促生存作用

细胞外 ATP 通过激活质膜定位的嘌呤能受体作为自分泌和/或旁分泌信号分子起作用。嘌呤能 P2X7 受体 (P2X7R) 的刺激会增加胞质 Ca 2+ ([Ca 2+ ] c ),进而激活 Pannexin 1 (Panx1) 通道。在早期的研究中,Panx1 和 P2X7R 已被证明具有物理相互作用。此外,这两个通道都涉及类似的病理生理过程。在这项研究中,我们研究了 Panx1 对 P2X7R 介导的 Ca 2+流入的影响。Panx1 减弱了 P2X7R 介导的 [Ca 2+ ] c在 CHO-K1 和 HEK-293 细胞中的升高。[Ca 2+ ] cPanx1 敲低星形胶质细胞的上升幅度更高。Panx1 阻滞剂carbenoxolone 的存在不影响抑制作用。发现 Panx1 羧基末端 (CT) 第 350 和第 386 个氨基酸残基之间的区域对于抑制 P2X7R 至关重要。与全长 Panx1 一样,单独的 CT(第 350 至第 426 个氨基酸)能够减弱 [Ca 2+ ] c的升高。此外,CT 防止了由 P2X7R 过度激活引起的细胞死亡。基于我们的研究结果,我们提出了 Panx1 通过调节 P2X7R 发挥的一种新的促生存作用。

更新日期:2021-09-01
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