胆固醇及其氧化衍生物对人红细胞钙通道的立体特异性调节。
Stereospecific modulation of the calcium channel in human erythrocytes by cholesterol and its oxidized derivatives.
作者信息
Neyses L, Locher R, Stimpel M, Streuli R, Vetter W
出版信息
Biochem J. 1985 Apr 1;227(1):105-12. doi: 10.1042/bj2270105.
To study the effect of cholesterol and its pathophysiologically important oxidized derivatives (OSC) on the calcium entry channel, the human red blood cell was used as a model system. The calcium ejecting adenosinetriphosphatase (ATPase) was inhibited by vanadate. The cells were loaded with OSC at concentrations between 1.25 X 10(-5) and 25 X 10(-5) mol/l. 22-Hydroxycholesterol, cholestan-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol,3 beta,5 alpha-dihydroxycholestan-6-one and 3 beta-hydroxy-5 alpha-cholestan-7-one stimulated 45Ca2+ influx by up to almost 90%, whereas 25-hydroxycholesterol, 7 beta-hydroxycholesterol, 20 alpha-hydroxycholesterol and 7-oxocholesterol inhibited influx by up to 75%. Both stimulation and inhibition were dependent on the amount of OSC incorporated into the membrane. More than 90% of the total modification of calcium influx by OSC was accounted for by an influence on the nitrendipine-inhibitable part of influx. Enrichment of cholesterol in the membrane greatly stimulated, and cholesterol depletion inhibited, Ca2+ influx. These results demonstrate that cholesterol and its oxidized derivatives are able to modulate the calcium channel in human red blood cells in a highly stereospecific manner.
为了研究胆固醇及其具有病理生理学重要意义的氧化衍生物（OSC）对钙内流通道的影响，将人类红细胞用作模型系统。钒酸盐抑制了钙排出型三磷酸腺苷酶（ATPase）。细胞被加载了浓度在1.25×10⁻⁵至25×10⁻⁵摩尔/升之间的OSC。22-羟基胆固醇、胆甾烷-3β,5α,6β-三醇、5α-胆甾烷-3β-醇、3β,5α-二羟基胆甾烷-6-酮和3β-羟基-5α-胆甾烷-7-酮刺激45Ca²⁺内流高达近90%，而25-羟基胆固醇、7β-羟基胆固醇、20α-羟基胆固醇和7-氧代胆固醇抑制内流高达75%。刺激和抑制都取决于掺入膜中的OSC的量。OSC对钙内流的总调节作用中，超过90%是通过对尼群地平可抑制的内流部分的影响来实现的。膜中胆固醇的富集极大地刺激了Ca²⁺内流，而胆固醇的耗尽则抑制了Ca²⁺内流。这些结果表明，胆固醇及其氧化衍生物能够以高度立体特异性的方式调节人类红细胞中的钙通道。
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