硒化合物通过氧化功能性硫醇来调节兔骨骼肌的钙释放通道/雷诺丁受体。

Selenium compounds modulate the calcium release channel/ryanodine receptor of rabbit skeletal muscle by oxidizing functional thiols.

作者信息

Xia Ruohong, Ganther Howard E, Egge Adam, Abramson Jonathan J

机构信息

Physics Department, East China Normal University, 3663 Zhongshan North Road, Shanghai 200062, China.

出版信息

Biochem Pharmacol. 2004 Jun 1;67(11):2071-9. doi: 10.1016/j.bcp.2004.02.018.

DOI:10.1016/j.bcp.2004.02.018

PMID:15135304

Abstract

Selenium compounds, such as sodium selenite and Ebselen were shown to increase high affinity ryanodine binding to the skeletal muscle type ryanodine receptor (RyR1) at nanomolar concentrations, and inhibit the receptor at low micromolar concentrations. This biphasic response was observed in both concentration and time-dependent assays. Extensive washing did not reverse either the stimulation or suppression of receptor binding, but both were prevented or reversed by addition of reduced glutathione, GSH. Selenium compounds were also shown to induce Ca(2+) release from the isolated sarcoplasmic reticulum vesicles. Sodium selenite and Ebselen stimulated the skeletal muscle ryanodine receptor by oxidizing 14 of 47 free thiols per monomer on RyR1 (as detected with the alkylating agent 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin) (CPM). Oxidation of the remaining thiols by these selenium compounds resulted in inhibition of the ryanodine receptor.

摘要

硒化合物，如亚硒酸钠和依布硒仑，已表明在纳摩尔浓度下可增加高亲和力的ryanodine与骨骼肌型ryanodine受体（RyR1）的结合，并在低微摩尔浓度下抑制该受体。在浓度和时间依赖性试验中均观察到这种双相反应。大量洗涤不能逆转对受体结合的刺激或抑制，但加入还原型谷胱甘肽（GSH）可防止或逆转这两种情况。硒化合物还显示可诱导从分离的肌浆网囊泡中释放Ca(2+)。亚硒酸钠和依布硒仑通过氧化RyR1上每个单体47个游离巯基中的14个（用烷基化剂7-二乙氨基-3-(4'-马来酰亚胺基苯基)-4-甲基香豆素（CPM）检测）来刺激骨骼肌ryanodine受体。这些硒化合物对其余巯基的氧化导致ryanodine受体受到抑制。