Mitochondria a key role in microcystin-LR kidney intoxication
Mitochondria a key role in microcystin-LR kidney intoxication
复制标题
DOI：
10.1002/jat.1251
复制
发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Peixoto, F. P.
中科院分区：
文献类型：
--
作者：
La-Salete, R.;Oliveira, M. M.;Peixoto, F. P.
微囊藻毒素（microcystiins, MCs）是一组密切相关的环七肽，由多种常见的蓝藻产生。这些毒素与人类和牲畜的死亡有关。微囊藻毒素- lr可通过改变血管、肾小球和泌尿参数影响肾脏生理，表明MC-LR可直接作用于肾脏。本研究旨在探讨MC-LR对大鼠肾脏离体线粒体氧化磷酸化的影响。此外，微囊藻毒素- lr降低了状态3和羰基氰化物对三氟甲氧基苯腙（FCCP）不耦合呼吸。MC-LR以浓度依赖性的方式强烈抑制跨膜电位，表明存在解耦效应；然而，微囊藻毒素lr并没有增加线粒体内膜对质子的通透性。因此，跨膜减少是对氧化还原复合物的强烈抑制作用的结果。将解偶联浓度的MC-LR添加到钌红处理的Ca2+负载线粒体中，导致线粒体通透性过渡孔（MPTP）开放，线粒体在等渗蔗糖培养基中肿胀。环孢素A可阻止Ca2+存在下的线粒体肿胀，过氧化氢酶和二硫苏糖醇可显著抑制线粒体肿胀，表明线粒体产生的活性氧参与了这一过程。从本研究可以得出结论，微囊藻毒素- lr促进的生物能损伤似乎足以解释肾损伤。版权所有(C) 2007约翰威利父子有限公司
Microcystins (MCs) are a group of closely related cyclic heptapeptides produced by a variety of common cyanobacteria. These toxins have been implicated in both human and livestock mortality. Microcystin-LR could affect renal physiology by altering vascular, glomerular and urinary parameters, indicating that MC-LR could act directly on the kidney. The aim of the current work was to examine the effect of MC-LR on mitochondrial oxidative phosphorylation of rat kidney isolated mitochondria.Furthermore, microcystin-LR decreased both state 3 and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)uncoupled respiration. The transmembrane potential was strongly depressed by MC-LR in a concentration dependent manner, pointing to an uncoupling effect; however, microcystin-LR did not increase the permeability of the inner mitochondria membrane to protons. Therefore, the transmembrane decrease was a consequence of a strong inhibitory effect on redox complexes. The addition of uncoupling concentrations of MC-LR to Ca2+-loaded mitochondria treated with ruthenium red resulted in mitochondrial permeability transition pore (MPTP) opening, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Mitochondrial swelling in the presence of Ca2+ was prevented by cyclosporin A and was drastically inhibited by catalase and dithiothreitol, indicating the participation of mitochondrial generated reactive oxygen species in this process. From this study it can be concluded that the bioenergetic lesion promoted by microcystin-LR seems to be sufficient to explain renal injury. Copyright (C) 2007 John Wiley & Sons, Ltd.