Selenium compounds modulate the calcium release channel/ryanodine receptor of rabbit skeletal muscle by oxidizing functional thiols.
Selenium compounds modulate the calcium release channel/ryanodine receptor of rabbit skeletal muscle by oxidizing functional thiols.
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DOI：
10.1016/j.bcp.2004.02.018
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发表时间：
2004-06
影响因子：
5.8
通讯作者：
Ruohong Xia;H. Ganther;Adam Egge;J. Abramson
中科院分区：
文献类型：
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作者：
Ruohong Xia;H. Ganther;Adam Egge;J. Abramson
硒化合物，如亚硒酸钠和依布硒啉，显示出在纳摩尔浓度下增加与骨骼肌型兰尼碱受体（RyR 1）的高亲和力兰尼碱结合，并在低微摩尔浓度下抑制受体。在浓度和时间依赖性测定中均观察到这种双相反应。广泛的洗涤并没有逆转受体结合的刺激或抑制，但两者都被阻止或通过添加还原型谷胱甘肽，GSH逆转。硒化合物也显示出诱导钙离子从分离的肌浆网囊泡释放。亚硒酸钠和依布硒啉通过氧化RyR 1上每个单体的47个游离巯基中的14个（用烷化剂7-二乙基氨基-3-（4′-马来酰亚胺基苯基）-4-甲基香豆素检测）（CPM）刺激骨骼肌兰尼碱受体。这些硒化合物对剩余硫醇的氧化导致兰尼碱受体的抑制。
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 Ca2+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.