Effects of the pyrrolizidine alkaloid senecionine and the alkenals trans-4-OH-hexenal and trans-2-hexenal on intracellular calcium compartmentation in isolated hepatocytes.
Effects of the pyrrolizidine alkaloid senecionine and the alkenals trans-4-OH-hexenal and trans-2-hexenal on intracellular calcium compartmentation in isolated hepatocytes.
复制标题
吡咯里西啶生物碱千里光碱和烯醛反式-4-OH-己烯醛和反式-2-己烯醛对离体肝细胞细胞内钙区室的影响。
DOI：
10.1016/0006-2952(89)90377-8
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发表时间：
1989
影响因子：
5.8
通讯作者：
Segall,HJ
中科院分区：
文献类型：
--
作者：
Griffin,DS;Segall,HJ
研究表明，吡咯里西定生物碱千里光碱可引起肝细胞胞浆游离钙浓度升高，这与细胞毒性增加有关。细胞毒性在无细胞外钙离子时比有细胞外钙离子时强，提示细胞内钙离子分布的改变，而不是细胞外钙离子的内流，是导致千里光碱肝毒性的原因。本文研究了千里光碱对游离肝细胞线粒体和线粒体外钙离子的作用，以及千里光碱的微粒体代谢物反式-4-羟基己烯醛(t-4HH)和相关的烯醛(反式-2-己烯醛)对线粒体和线粒体外室钙离子隔离的影响。每个测试化合物都引起线粒体外可用钙存储的减少，这一减少可被硫基还原剂二硫苏糖醇预先抑制。千里光碱和t-4HH可降低肝细胞线粒体内钙离子滞留水平。吡啶核苷酸还原剂β-羟丁酸酯的存在抑制了这种还原。这些结果表明，千里光甲素和t-4HH可能分别通过灭活游离巯基和氧化吡啶核苷酸来抑制线粒体外和线粒体内钙离子的滞留。
The pyrrolizidine alkaloid senecionine has been shown to produce an increase in cytosolic free Ca2+concentration in isolated hepatocytes that correlated with an increase in cellular toxicity. The cytotoxicity was greater in the absence of extracellular Ca2+than in its presence, suggesting that alterations in intracellular Ca2+distribution, and not an influx of extracellular Ca2+, were responsible for the senecionine-induced hepatotoxicity. The effect of senecionine, as well as the effects oftrans-4-OH-hexenal (t-4HH), a microsomal metabolite of senecionine, and a related alkenal, (trans-2-hexenal, on the sequestration of Ca2+in mitochondrial and extramitochondrial compartments were examined in isolated hepatocytes. Each of the test compounds elicited a decrease in the available extramitochondrial Ca2+stores that was inhibited by pretreatment with the thiol group reducing agent, dithiothreitol. Senecionine and t-4HH decreased the level of Ca2+sequestered in the mitochondrial compartment of hepatocytes. The presence of a pyridine nucleotide reducing agent, β-hydroxybutyrate, inhibited this reduction. These results suggest that both senecionine and t-4HH inhibit the sequestration of Ca2+in extramitochondrial and mitochondrial compartments possibly by inactivating free sulfhydryl groups and oxidizing pyridine nucleotides respectively.