Nitric oxide protects the skeletal muscle Ca2+ release channel from oxidation induced activation
Nitric oxide protects the skeletal muscle Ca2+ release channel from oxidation induced activation
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DOI：
10.1074/jbc.272.41.25462
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发表时间：
1997-10-10
影响因子：
4.8
通讯作者：
Hamilton, SL
中科院分区：
文献类型：
--
作者：
Aghdasi, B;Reid, MB;Hamilton, SL
活性氧中间体和一氧化氮可能通过与 Ca2+ 释放通道直接相互作用来调节骨骼肌纤维的收缩功能，氧化剂在 Ca2+ 释放通道四聚体的亚基之间产生二硫键，这伴随着通道活性的增加。 巯基烷基化剂 N-乙基马来酰亚胺对 Ca2+ 释放通道活性具有三种不同的影响：首先，通道活性降低（第 1 阶段）；然后，随着持续暴露，活性显着增加（第 2 阶段）；最后，通道再次被抑制（第 3 阶段）（Aghdasi, B.、Zhang, J. Z.、Wu, Y.、Reid, M. B. 和 Hamilton, S. L., (1997) J. Biol. Chem. 272, 3739-3749）。 H2O2 和一氧化氮 (NO) 都会阻断 N-乙基马来酰亚胺的 1 相抑制作用。 NO 供体在对通道活性没有可检测到的影响的浓度下，会阻断亚基间交联并防止二硫键诱导剂二酰胺激活通道。这些发现支持 NO 通过防止调节性巯基氧化来调节 Ca2+ 释放通道活性的模型。然而，较高浓度的 NO 供体会激活通道并产生亚基间交联，支持 NO 对通道活性的双功能效应。低 NO 浓度可防止 Ca2+ 释放通道的氧化，而较高浓度则会氧化它。
Reactive oxygen intermediates and nitric oxide modulate the contractile function of skeletal muscle fibers, possibly via direct interaction with the Ca2+ release channel, Oxidants produce disulfide bonds between subunits of the Ca2+ release channel tetramer, and this is accompanied by an increase in channel activity, The sulfhydryl alkylating agent N-ethylmaleimide has three distinct effects on Ca2+ release channel activity: first, channel activity is decreased (phase 1); then with continued exposure the activity is dramatically increased (phase 2); and finally, the channel is again inhibited (phase 3) (Aghdasi, B., Zhang, J. Z., Wu, Y., Reid, M. B., and Hamilton, S. L., (1997) J. Biol. Chem. 272, 3739-3749). Both H2O2 and nitric oxide (NO) block the phase 1 inhibitory effect of N-ethylmaleimide. NO donors, at concentrations that have no detectable effect on channel activity, block intersubunit cross-linking and prevent activation of the channel by the disulfide inducing agent, diamide, These findings support a model in which NO modulates the activity of the Ca2+ release channel by preventing oxidation of regulatory sulfhydryls. However, higher concentrations of NO donors activate the channel and produce intersubunit cross-links, supporting a bifunctional effect of NO on channel activity, Low NO concentrations prevent oxidation of the Ca2+ release channel whereas higher concentrations oxidize it.