首页> 美国卫生研究院文献>Biochemical Journal >Partial inhibition by cyclosporin A of the swelling of liver mitochondria in vivo and in vitro induced by sub-micromolar Ca2+ but not by butyrate. Evidence for two distinct swelling mechanisms.
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Partial inhibition by cyclosporin A of the swelling of liver mitochondria in vivo and in vitro induced by sub-micromolar Ca2+ but not by butyrate. Evidence for two distinct swelling mechanisms.

机译:亚微摩尔Ca2 +引起的环孢菌素A部分抑制体内和体外肝脏线粒体的肿胀但不引起丁酸盐的抑制。有两种不同的溶胀机制的证据。

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摘要

1. The effects of cyclosporin A on the increase in matrix PPi and consequent swelling of energized liver mitochondria incubated with 1 mM-butyrate, 30 microM-bongkrekic acid or 0.1-35 microM-Ca2+ [Halestrap (1989) Biochim. Biophys. Acta 973, 355-382] were studied. 2. Cyclosporin (1 microM) had no significant effect on the swelling induced by butyrate, bongkrekic acid or Ca2+ at concentrations of less than 0.3 microM. 3. At higher [Ca2+] (greater than 0.3 microM), swelling became progressively inhibited by cyclosporin, although the increase in matrix PPi was slightly greater in the presence than in the absence of cyclosporin. 4. Titration with cyclosporin indicated that there are 128 pmol of relevant cyclosporin-binding sites per mg of mitochondrial protein, with a Ki of about 5 nM. 5. The decrease in light-scattering by hepatocytes induced by butyrate [Davidson & Halestrap (1988) Biochem. J. 254, 379-384] was unaffected by cyclosporin, whereas that induced by vasopressin was inhibited by 20-30% without a significant change in cellular PPi content. 6. It is suggested that there are two mechanisms for the increase in mitochondrial volume induced by Ca2+: a PPi-mediated mechanism that is insensitive to cyclosporin and an additional Ca2(+)-mediated effect that is inhibited by cyclosporin. The nature of these pathways and their inter-relationship is discussed in the following paper [Halestrap & Davidson (1990) Biochem. J. 268, 153-160].
机译:1.环孢菌素A对基质PPi的增加以及随后与1 mM丁酸酯,30 microM奉克酸或0.1-35 microM-Ca2 +孵育的充满活力的肝线粒体肿胀的影响[Halestrap(1989)Biochim。生物物理学。研究学报973,355-382]。 2.环孢菌素(1 microM)对丁酸,邦克雷酸或Ca2 +浓度小于0.3 microM引起的肿胀没有明显影响。 3.在较高的[Ca2 +](大于0.3 microM)下,环孢菌素逐渐溶胀,尽管存在时基质PPi的增加比不存在环孢菌素时的增加。 4.用环孢菌素滴定表明,每毫克线粒体蛋白有128 pmol相关环孢菌素结合位点,Ki约为5 nM。 5.由丁酸盐诱导的肝细胞光散射的减少[Davidson&Halestrap(1988)Biochem。 J. 254,379-384]不受环孢菌素的影响,而由加压素诱导的抑制作用被抑制20-30%,而细胞PPi含量没有明显变化。 6.建议存在由Ca2 +引起的线粒体体积增加的两种机制:对环孢菌素不敏感的PPi介导的机制和由环孢菌素抑制的另一种Ca2(+)介导的作用。这些途径的性质及其相互关系在以下论文中讨论[Halestrap&Davidson(1990)Biochem。 J. 268,153-160]。

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