Regulation of acid-sensing ion channel 1a function by tissue kallikrein may be through channel cleavage
Regulation of acid-sensing ion channel 1a function by tissue kallikrein may be through channel cleavage
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组织激肽释放酶可能通过通道裂解来调节酸敏感离子通道 1a 功能
DOI：
10.1016/j.neulet.2010.12.023
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发表时间：
2011
影响因子：
2.5
通讯作者：
Q. Dong
中科院分区：
文献类型：
--
作者：
Jingjing Su;Yuping Tang;Ling Liu;HouGuang Zhou;Q. Dong
最近，我们已经证明丝氨酸蛋白酶组织激肽释放酶（TK）可以保护皮层神经元免受缺血-酸中毒/再灌注诱导的损伤，这种作用可能是由酸敏感离子通道（ASIC）介导的。然而，关于TK如何调节ASIC的功能知之甚少。在这里，我们提供的证据表明，ASIC1a功能的调节TK可能与其切割。高浓度TK（3 μ M）部分切割ASIC1a的细胞外环，随后LDH释放显著减少，pH 6.2时细胞存活率增加。用蛋白酶抑制剂抑肽酶预处理抑制了ASIC1a的裂解，并阻止了TK的功能调节。然而，未观察到未被TK功能性修饰的ASIC2a的切割。因此，我们认为ASIC1a细胞外环的有限蛋白水解可能是TK调控ASIC1a功能的潜在机制之一。
Recently, we have demonstrated that serine protease tissue kallikrein (TK) can protect cortical neurons against ischemia-acidosis/reperfusion-induced injury, and that this effect might be mediated by acid-sensing ion channels (ASICs). However, little is known about how TK regulates the function of ASICs. Here we provided evidence that the regulation of ASIC1a function by TK was probably correlated with its cleavage. High concentration of TK (3μM) partially cleaved the extracellular loop of ASIC1a, followed by a marked decrease of LDH release and an increase of cell survival at pH 6.2. Pretreatment with a protease inhibitor aprotinin inhibited the cleavage of ASIC1a and prevented functional regulation by TK. However, the cleavage of ASIC2a, which was not functionally modified by TK, was not observed. Therefore, we propose that the limited proteolysis of extracellular loop within ASIC1a might be one of the potential regulatory mechanisms of ASIC1a function by TK.
鉴定脑中和脑 mRNA 编码的无细胞翻译产物中的组织激肽释放酶。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Chao,J;Woodley,C;Chao,L;Margolius,HS
通讯作者：
Margolius,HS
人体组织激肽释放酶对含有 Phe-Phe 氨基酸对的底物的特异性。
DOI：
--
发表时间：
1999
期刊：
The Biochemical journal
影响因子：
--
作者：
Pimenta,DC;Chao,J;Chao,L;Juliano,MA;Juliano,L
通讯作者：
Juliano,L
影响因子：
--
作者：
NEDERGAARD, M;KRAIG, RP;PULSINELLI, WA
通讯作者：
PULSINELLI, WA