Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes.
Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes.
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DOI：
10.1038/cddis.2013.341
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发表时间：
2013-10-03
影响因子：
9
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氧化应激导致视神经乳头（ONH）胶质细胞功能障碍。然而，线粒体在这种功能障碍中的确切功能作用的生物学基础尚未完全了解。辅酶Q10（CoQ 10）是电子传递链的重要辅因子，是一种有效的抗氧化剂，通过清除活性氧（ROS）保护神经细胞免受氧化应激的影响。在这里，我们测试了过氧化氢（100 μM H2 O2）诱导的氧化应激是否改变了线粒体网络，氧化磷酸化（OXPHOS）复合物（Cx）表达和生物能量学，以及辅酶Q10是否可以改善体外ONH星形胶质细胞线粒体中氧化应激介导的改变。氧化应激可激活ONH星形胶质细胞，上调超氧化物歧化酶2（SOD 2）和血红素加氧酶-1（HO-1）蛋白表达。与此相反，辅酶Q10不仅阻止了ONH星形胶质细胞的活化，而且还显著降低了ONH星形胶质细胞中SOD 2和HO-1蛋白的表达以对抗氧化应激。此外，辅酶Q10通过增加线粒体数量和体积密度以及通过保护线粒体嵴结构来防止线粒体质量的显著损失，以及促进ONH星形胶质细胞中的丝裂素和过氧化物酶体增殖物激活受体-γ共激活因子-1蛋白表达，这表明诱导线粒体生物发生。最后，氧化应激引发OXPHOS Cx蛋白表达的上调，以及减少细胞三磷酸腺苷（ATP）的生产和增加ROS的产生在ONH星形细胞。然而，辅酶Q10保留了OXPHOS蛋白表达和细胞ATP产生，以及减少了ONH星形胶质细胞中ROS的产生。基于这些观察，我们认为氧化应激介导的线粒体功能障碍或改变可能是ONH星形胶质细胞功能障碍的重要病理生理机制。辅酶Q10可能为保护ONH星形胶质细胞免受氧化应激介导的线粒体功能障碍或青光眼和其他视神经病变的改变提供新的治疗潜力和策略。
Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies.