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肌浆网对钙蓄积的抑制作用:阿霉素心脏毒性的一种假定机制。

Inhibition of calcium accumulation by the sarcoplasmic reticulum: a putative mechanism for the cardiotoxicity of adriamycin.

作者信息

Halili-Rutman I, Hershko C, Link G, Rutman A J, Shainberg A

机构信息

The Otto Meyerhoff Drug Receptor Center, Department of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

出版信息

Biochem Pharmacol. 1997 Jul 1;54(1):211-4. doi: 10.1016/s0006-2952(97)00108-1.

DOI:10.1016/s0006-2952(97)00108-1
PMID:9296369
Abstract

The aim of this study was to examine the effect of adriamycin (ADR) on calcium accumulation by the sarcoplasmic reticulum (SR). Chemical skinning of cultured rat myocardial cells compromised the barrier function of the cell membrane and thus permitted direct exposure of mitochondrial and non-mitochondrial sites to ADR. In the presence of ATP, and sodium azide, mitochondrial calcium accumulation was negligible. Furthermore, it has previously been shown that non-mitochondrial calcium accumulation is mediated mainly by the SR under these conditions. Incubation with 10 microM ADR for 2 hr reduced the level of calcium accumulation by the SR by 50%. A similar effect was obtained after 24 hr incubation with 1 microM ADR. The addition of ferric iron to the culture medium further reduced the level of calcium accumulation. Neither vitamin E nor beta-carotene affected calcium accumulation by the SR. These results suggest that ADR interferes with the calcium accumulation activity of the SR and that ferric iron potentiates this effect.

摘要

本研究的目的是检测阿霉素(ADR)对肌浆网(SR)钙蓄积的影响。培养的大鼠心肌细胞化学去膜破坏了细胞膜的屏障功能,从而使线粒体和非线粒体部位直接暴露于ADR。在ATP和叠氮化钠存在的情况下,线粒体钙蓄积可忽略不计。此外,先前已经表明,在这些条件下非线粒体钙蓄积主要由SR介导。用10微摩尔ADR孵育2小时可使SR的钙蓄积水平降低50%。用1微摩尔ADR孵育24小时后获得了类似的效果。向培养基中添加三价铁进一步降低了钙蓄积水平。维生素E和β-胡萝卜素均未影响SR的钙蓄积。这些结果表明,ADR干扰SR的钙蓄积活性,并且三价铁增强了这种作用。

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