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珍珠鸡(Numida meleagris)肝脏线粒体内膜的钙依赖性非特异性通透性。

Ca(2+)-dependent nonspecific permeability of the inner membrane of liver mitochondria in the guinea fowl (Numida meleagris).

作者信息

Vedernikov Aleksander A, Dubinin Mikhail V, Zabiakin Vladimir A, Samartsev Victor N

机构信息

Mari State University, pl. Lenina 1, Yoshkar-Ola, Mari El, 424001, Russia.

出版信息

J Bioenerg Biomembr. 2015 Jun;47(3):235-42. doi: 10.1007/s10863-015-9606-z. Epub 2015 Feb 18.

Abstract

This comparative study presents the results of the induction of Ca(2+)-dependent nonspecific permeability of the inner membrane (pore opening) of rat and guinea fowl liver mitochondria by mechanisms that are both sensitive and insensitive to cyclosporin A (CsA). It was established that energized rat and guinea fowl liver mitochondria incubated with 1 mM of inorganic phosphate (Pi) are capable of swelling upon addition of at least 125 and 875 nmol of CaCl2 per 1 mg protein, respectively. Under these conditions, the Ca(2+) release from the mitochondria of these animals and a drop in Δψ are observed. All of these processes are inhibited by 1 μM of CsA. FCCP, causing organelle de-energization, induces pore opening in rat and guinea fowl liver mitochondria upon addition of 45 и 625 nmol of CaCl2 per 1 mg protein, respectively. These results suggest the existence of a CsA-sensitive mechanism for the induction of Ca(2+)-dependent pores in guinea fowl liver mitochondria, which has been reported in rat liver mitochondria. However, guinea fowl liver mitochondria have a significantly greater resistance to Ca(2+) as a pore inducer compared to rat liver mitochondria. It was found that the addition of α,ω-hexadecanedioic acid (HDA) to rat and guinea fowl liver mitochondria incubated with CsA and loaded with Ca(2+) causes organelle swelling and Ca(2+) release from the matrix. It is assumed that in contrast to the CsA-sensitive pore, the CsA-insensitive pore induced by HDA in the inner membrane of guinea fowl liver mitochondria, as well as in rat liver mitochondria, is lipid in nature.

摘要

这项比较研究展示了通过对环孢菌素A(CsA)敏感和不敏感的机制,诱导大鼠和珍珠鸡肝脏线粒体内膜Ca(2+)依赖性非特异性通透性(孔开放)的结果。结果表明,用1 mM无机磷酸盐(Pi)孵育的有活力的大鼠和珍珠鸡肝脏线粒体,分别在每1 mg蛋白质添加至少125和875 nmol CaCl2后能够肿胀。在这些条件下,观察到这些动物线粒体中Ca(2+)的释放以及Δψ的下降。所有这些过程都受到1 μM CsA的抑制。FCCP导致细胞器去能,分别在每1 mg蛋白质添加45和625 nmol CaCl2后,诱导大鼠和珍珠鸡肝脏线粒体中的孔开放。这些结果表明,珍珠鸡肝脏线粒体中存在一种对CsA敏感的机制来诱导Ca(2+)依赖性孔,这在大鼠肝脏线粒体中已有报道。然而,与大鼠肝脏线粒体相比,珍珠鸡肝脏线粒体对作为孔诱导剂的Ca(2+)具有显著更高的抗性。研究发现,向用CsA孵育并加载了Ca(2+)的大鼠和珍珠鸡肝脏线粒体中添加α,ω-十六烷二酸(HDA)会导致细胞器肿胀和Ca(2+)从基质中释放。据推测,与对CsA敏感的孔不同,HDA在珍珠鸡肝脏线粒体内膜以及大鼠肝脏线粒体内膜中诱导的对CsA不敏感的孔本质上是脂质的。

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