Na+-independent release of Ca2+ from rat heart mitochondria. Induction by adriamycin aglycone.
Na+-independent release of Ca2+ from rat heart mitochondria. Induction by adriamycin aglycone.
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大鼠心脏线粒体Ca2+不依赖于Na的释放。
DOI：
10.1016/0006-2952(88)90165-7
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发表时间：
1988
影响因子：
5.8
通讯作者：
Shinaberry,RG
中科院分区：
文献类型：
--
作者：
Sokolove,PM;Shinaberry,RG
研究阿霉素苷元对大鼠心肌线粒体钙离子滞留的影响。7-羟基苷元(5-20μM)在经过一段随药物浓度增加而减小的初始滞后后，引发钙离子释放。苷元诱导的Ca~(2+)释放与依赖于Ca~(2+)的线粒体肿胀，依赖于Ca~(2+)的线粒体膜电位的崩溃，依赖于Ca~(2+)的线粒体吡啶核苷酸的氧化，以及从浓缩构型向正态构型的转变有关。地布卡因、二硫苏糖醇、三磷酸腺苷和牛血清白蛋白可抑制苷元诱导的钙释放。因此，可以得出结论，苷元诱导的钙释放反映了线粒体内膜对分子量为<；1000的溶质的通透性随钙的增加，这一点已经在其他触发剂[R.A.Haworth和D.R.Hunter，Archs Biochem]中观察到。《生物物理学》195,460(1979)；I.Al-Nasser和M.Crompton，Biochem。J.239，19(1986)]。尤其是，7-羟基苷元减少了引发通透性增加所需的钙离子的量。苷元对钙摄取无明显影响。阿霉素更显著的生物代谢产物7-脱氧阿霉素苷元在诱导钙释放方面也有类似的作用，而且两种苷元的作用都比母药强很多。阿霉素及其相关的蒽环类药物是有效的抗肿瘤药物，但其严重的心脏毒性限制了其临床应用。这些结果表明，苷元的形成以及由此引起的细胞内钙稳态和代谢物区域化的破坏可能介导了蒽环类药物的心脏毒性。
The effect of adriamycin aglycones on Ca2+retention by isolated, preloaded rat heart mitochondria was assessed. After an initial lag, which decreased with increasing drug concentration, the 7-hydroxy-aglycone (5–20 μM) triggered Ca2+release. Aglycone-induced Ca2+release was correlated with Ca2+-dependent mitochondrial swelling, Ca2+-dependent collapse of the mitochondrial membrane potential, Ca2+-dependent oxidation of mitochondrial pyridine nucleotides, and a transition from the condensed to the orthodox configuration. Aglycone-induced Ca2+release was inhibited by dibucaine, dithiothreitol, ATP, and bovine serum albumin. It can be concluded, therefore, that aglycone-induced Ca2+release reflects the Ca2+-dependent increase in the permeability of the inner mitochondrial membrane to solutes of molecular weight < 1000 which has been observed with other triggering agents [R. A. Haworth and D. R. Hunter,Archs Biochem. Biophys.195, 460 (1979); I. Al-Nasser and M. Crompton,Biochem. J.239, 19 (1986)]. In particular, the 7-hydroxy-aglycone decreased the amount of Ca2+required to trigger the permeability increase. No effect of the aglycone on Ca2+uptake could be discerned. 7-Deoxy-adriamycin aglycone, the more prominent biological metabolite of adriamycin, was similarly effective in inducing Ca2+release, and both aglycones were substantially more effective than the parent drug. Adriamycin and related anthracyclines are potent antineoplastic agents, the clinical use of which is limited by severe cardiotoxicity. These results suggest that aglycone formation and the resultant disruption of both cellular Ca2+homeostasis and metabolite compartmentation may mediate anthracycline cardiotoxicity.
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大鼠肝线粒体中积累的 CA 的稳态维持。
影响因子：
4.8
作者：
Z. Drahota;E. Carafoli;C. Rossi;R. L. Gamble;A. Lehninger
通讯作者：
A. Lehninger
DOI：
10.1016/s0021-9258(17)43600-3
发表时间：
1984-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. C. Beatrice;D. L. Stiers;D. Pfeiffer
通讯作者：
M. C. Beatrice;D. L. Stiers;D. Pfeiffer
叙利亚金色仓鼠中柔红霉素和阿霉素的代谢
DOI：
10.1016/0006-2944(73)90040-9
发表时间：
1973
期刊：
Biochemical Medicine
影响因子：
--
作者：
N. Bachur;M. Egorin;R. C. Hildebrand
通讯作者：
R. C. Hildebrand
大鼠肝微粒体对柔红霉素苷元的生物转化。
影响因子：
11.2
作者：
Schwartz,HS;Paul,B
通讯作者：
Paul,B
影响因子：
5.8
作者：
Gewirtz,DA;Yanovich,S
通讯作者：
Yanovich,S