SOD1 and MitoTEMPO partially prevent mitochondrial permeability transition pore opening, necrosis, and mitochondrial apoptosis after ATP depletion recovery.
SOD1 and MitoTEMPO partially prevent mitochondrial permeability transition pore opening, necrosis, and mitochondrial apoptosis after ATP depletion recovery.
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DOI：
10.1016/j.freeradbiomed.2010.08.018
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发表时间：
2010-11-30
影响因子：
7.4
通讯作者：
Nilakantan V
中科院分区：
文献类型：
--
作者：
Liang HL;Sedlic F;Bosnjak Z;Nilakantan V
在肾缺血再灌注损伤中，过量活性氧（ROS）的产生导致线粒体功能障碍、细胞凋亡和坏死。以前，我们表明，慢病毒载体介导的超氧化物歧化酶-1（SOD 1）在近端肾小管上皮细胞（LLC-PK 1）的过度表达，降低细胞毒性在体外模型的IR损伤。在这里，我们研究了SOD 1过表达对ATP耗竭-恢复（ATP-DR）后线粒体信号转导的影响。为了检查线粒体ROS的作用，用线粒体抗氧化剂MitoTEMPO处理一部分细胞。SOD 1和MitoTEMPO均能抑制ATP DR介导的线粒体[Ca 2 +]m升高、线粒体膜电位（Δ Cam）降低和线粒体通透性转换孔（MPTP）增加（P < 0.01）。SOD 1阻止ATP-DR诱导的线粒体Bax易位，尽管促凋亡蛋白从线粒体的释放不能被单独的SOD 1阻止，并且需要SOD 1和MitoTEMPO两者的存在。SOD 1抑制c-jun磷酸化的增加，表明JNK信号通过ROS调节Bax向线粒体的转位。ATP-DR介导的MPTP和线粒体信号的变化增加了坏死和凋亡，这两者都被SOD 1和MitoTEMPO部分减弱。这些研究表明，SOD 1和MitoTEMPO保持线粒体的完整性和减弱ATP-DR介导的坏死和凋亡。
Generation of excessive reactive oxygen species (ROS) leads to mitochondrial dysfunction, apoptosis and necrosis in renal ischemia-reperfusion (IR) injury. Previously we showed that lentiviral vector mediated over-expression of superoxide dismutase-1 (SOD1) in proximal tubular epithelial cells (LLC-PK1) reduced cytotoxicity in an in vitro model of IR injury. Here, we examined the effects of SOD1 over-expression on mitochondrial signaling following ATP depletion-recovery (ATP-DR). To examine the role of mitochondrial ROS, a subset of cells were treated with the mitochondrial antioxidant, MitoTEMPO. ATP-DR-mediated increases in mitochondrial calcium ([Ca2+]m), loss of mitochondrial membrane potential (ΔΨm) and increase in mitochondrial permeability transition pore (MPTP) were attenuated by SOD1 and MitoTEMPO (P < 0.01). SOD1 prevented ATP-DR induced mitochondrial Bax translocation, although the release of pro-apoptotic proteins from mitochondria was not prevented by SOD1 alone and required the presence of both SOD1 and MitoTEMPO. SOD1 suppressed the increase in c-jun phosphorylation suggesting that JNK signaling regulates Bax translocation to mitochondria via ROS. ATP-DR-mediated changes in MPTP and mitochondrial signaling increased necrosis and apoptosis, both of which were partially attenuated by SOD1 and MitoTEMPO. These studies show that SOD1 and MitoTEMPO preserve mitochondrial integrity and attenuate ATP-DR mediated necrosis and apoptosis.
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影响因子：
3.9
作者：
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通讯作者：
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