1,3-dinitrobenzene inhibits mitochondrial complex II in rat and mouse brainstem and cortical astrocytes
1,3-dinitrobenzene inhibits mitochondrial complex II in rat and mouse brainstem and cortical astrocytes
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DOI：
10.1016/s0161-813x(03)00031-7
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发表时间：
2003-06-01
期刊：
影响因子：
3.4
通讯作者：
Philbert, MA
中科院分区：
文献类型：
--
作者：
Phelka, AD;Beck, MJ;Philbert, MA
1，3-二硝基苯(DNB)在大鼠和小鼠中产生水肿性、胶质血管病变，最初局限于高能量需求的脑干核团。细胞内能量产生过程的扰动可诱导线粒体通透性转换孔(MtPTP)复合体的形成。脑干星形胶质细胞对DNB的选择性易感性是由环孢素A可抑制的线粒体通透性转变(MPT)孔的开放阈值比大脑皮层星形胶质细胞低10倍介导的。其他硝基化合物，如3-硝基丙酸，选择性地干扰局部能量代谢，包括线粒体琥珀酸脱氢酶活性。然而，DNB诱导的MPT的开始和星形胶质细胞中能量产生过程的中断之间的联系仍然不清楚。观察DNB对培养的新生大鼠、小鼠脑干和皮质星形胶质细胞琥珀酸脱氢酶活性的影响。组织化学和分光光度分析均证实，100um DNB作用于体外培养的大鼠脑干和皮质星形胶质细胞0.5、2和5h，SDH活性受到明显的时间抑制。CsA可显著降低DNB对脑干星形胶质细胞SDH活性的抑制作用，但两种抑制剂均不能降低DNB对皮层星形胶质细胞SDH活性的抑制作用。这些数据表明，DNB诱导的SDH抑制可能不依赖于星形胶质细胞中mtPTP复合体的差异区域激活，并且一种未知的环孢素A抑制因子介导了DNB诱导的SDH功能的丧失。(C)2003 Elsevier Science Inc.保留所有权利。
1,3-Dinitrobenzene (DNB) produces edematous, glio-vascular lesions that are initially confined to brainstem nuclei with high energy requirements in rats and mice. Perturbation of energy producing processes in the cell is known to induce formation of the mitochondrial permeability transition pore (mtPTP) complex. Selective vulnerability of brainstem astrocytes to DNB is mediated by a 10-fold lower threshold for opening of the cyclosporin A-inhibitable mitochondrial permeability transition (MPT) pore than their cortical counterparts. Other nitrocompounds, such as 3-nitropropionic acid, selectively interfere with regional energy metabolism, including mitochondrial succinate dehydrogenase activity. However the link between DNB-induced onset of the MPT and disruption of energy producing processes in the astrocyte remains unclear. The effects of DNB on succinate dehydrogenase activity were evaluated in cultured neonatal rat and mouse brainstem and cortical astrocytes. Both histochemical and spectrophotometric assays confirmed significant temporal inhibition of SDH activity in brainstem and cortical astrocytes 0.5, 2 and 5 h following exposure to 100 muM DNB in vitro. Although DNB-induced inhibition of SDH was significantly decreased by CsA pretreatment in brainstem astrocytes after 0.5 and 2 h and with a second pore inhibitor bongkrekic acid (BKA) after 5 h, both inhibitors failed to reduce inhibition of SDH activity in cortical astrocytes. These data suggest that DNB-induced inhibition of SDH may be independent of differential regional activation of the mtPTP complex in astrocytes and that an unidentified cyclosporin A-inhibitable factor mediates DNB-induced loss of SDH function. (C) 2003 Elsevier Science Inc. All rights reserved.