Effects of S-glutathionylation and S-nitrosylation on calmodulin binding to triads and FKBP12 binding to type 1 calcium release channels
Effects of S-glutathionylation and S-nitrosylation on calmodulin binding to triads and FKBP12 binding to type 1 calcium release channels
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DOI：
10.1089/ars.2005.7.870
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发表时间：
2005-07-01
影响因子：
6.6
通讯作者：
Hidalgo, C
中科院分区：
文献类型：
--
作者：
Aracena, P;Tang, WT;Hidalgo, C
本研究表明，谷胱甘肽（GSH）和过氧化氢（H2 0 2）联合作用可促进RyR 1钙释放通道的S-谷胱甘肽化，并证实了RyR 1钙释放通道与S-亚硝基谷胱甘肽（GSNO）联合的S-谷胱甘肽化和S-亚硝基化。此外，我们发现S-35标记的12 kDa FK 506结合蛋白（[S-35] FKBP 12）与三联体或重肌浆网囊泡中存在的RyR 1结合的Kd为13.1 nM;通过NOR-3或GSNO进行的RyR 1 S-亚硝基化，而不是S-谷胱甘肽化，特异性地增加了该Kd值的4 - 5倍。RyR 1氧化还原修饰也增加了[35 S]钙调蛋白结合三联体的Kd，而不影响B-max。RyR 1 S-谷胱甘肽化（由GSH加H2 O2诱导）或RyR 1 S-亚硝基化（由NOR-3产生）分别使脱辅基钙调蛋白（apoCaM）或Ca 2 +-钙调蛋白（CaCaM）与三联体结合的Kd增加约6倍或2倍。同样，GSNO诱导的RyR 1的S-谷胱甘肽化和S-亚硝基化使CaCaM与三联体结合的Kd增加了4倍，并消除了apoCaM结合。由于FKBP 12和CaCaM均抑制RyR 1，因此三联体制剂中FKBP 12与RyR 1的结合减少和/或CaCaM与RyR 1或二氢吡啶受体的结合减少可能导致报告的由S-谷胱甘肽化/S-亚硝基化介导的Ca 2+诱导的Ca 2+释放动力学活化增强。我们讨论了在生理或病理条件下这些氧化还原修饰对RyR 1介导的Ca 2+释放的可能后果。
This study shows that the combination of glutathione (GSH) plus hydrogen peroxide (H 2 0 2) promotes the S-glutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-nitrosoglutathione (GSNO). In addition, we show that S-35-labeled 12-kDa FK506-binding protein ([S-35]FKBP12) bound with a K-d of 13.1 nM to RyR1 present in triads or heavy sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S-glutathionylation, specifically increased by four- to fivefold this K-d value. RyR1 redox modifications also increased the K-d of [35S]calmodulin binding to triads without affecting B-max. RyR1 S-glutathionylation (induced by GSH plus H2O2) or RyR1 S-nitrosylation (produced by NOR-3) increased by approximately six- or twofold, respectively, the K-d of apocalmodulin (apoCaM) or Ca2+-calmodulin (CaCaM) binding to triads. Likewise, the combined S-glutathionylation and S-nitrosylation of RyR1 induced by GSNO increased by fourfold the Kd of CaCaM bindindg to triads and abolished apoCaM binding. As both FKBP12 and CaCaM inhibit RyR1, decreased FKBP12 binding to RyR1 and/or decreased CaCaM binding to either RyR1 or dihydropyridine receptor in triad preparations may cause the reported enhanced activation of Ca2+-induced Ca2+ release kinetics mediated by S-glutathionylation/S-nitrosylation. We discuss possible consequences of these redox modifications on RyR1-mediated Ca2+ release in physiological or pathological conditions.