Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy.
Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy.
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DOI：
10.1007/s00401-010-0697-7
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发表时间：
2010-10
影响因子：
12.7
通讯作者：
Feldman EL
中科院分区：
文献类型：
--
作者：
Vincent AM;Edwards JL;McLean LL;Hong Y;Cerri F;Lopez I;Quattrini A;Feldman EL
线粒体介导的高葡萄糖反应的氧化应激被认为是糖尿病神经病变发病机制中背根神经节（DRG）神经元损伤的主要原因。在本研究中，我们报告在完善的小鼠糖尿病神经病变模型中，有髓鞘和无髓鞘背根轴突中线粒体数量较多。在没有神经病变的年轻糖尿病动物或任何糖尿病动物的腹侧运动根中没有看到类似的变化。这些发现促使我们检查培养的 DRG 神经元神经突中响应高血糖的线粒体生物发生和裂变。我们通过 DRG 神经元和轴突中线粒体转录因子的增加和线粒体 DNA 的增加证明了线粒体的整体生物发生。然而，这一过程发生的时间比观察到的 DRG 神经突中线粒体数量的快速增加要长，而 DRG 神经突中线粒体数量的快速增加似乎至少部分是由线粒体裂变造成的。我们的结论是，在急性高血糖期间，线粒体裂变是一个突出的反应，过度的线粒体裂变可能导致能量产生失调、caspase 3 激活以及随后的 DRG 神经元损伤。在更长时间的高血糖期间，有证据表明轴突中存在代偿性线粒体生物发生。我们的数据表明线粒体生物发生和分裂之间的不平衡可能在糖尿病神经病变的发病机制中发挥作用。
Mitochondrial-mediated oxidative stress in response to high glucose is proposed as a primary cause of dorsal root ganglia (DRG) neuron injury in the pathogenesis of diabetic neuropathy. In the present study, we report a greater number of mitochondria in both myelinated and unmyelinated dorsal root axons in a well-established model of murine diabetic neuropathy. No similar changes were seen in younger diabetic animals without neuropathy or in the ventral motor roots of any diabetic animals. These findings led us to examine mitochondrial biogenesis and fission in response to hyperglycemia in the neurites of cultured DRG neurons. We demonstrate overall mitochondrial biogenesis via increases in mitochondrial transcription factors and increases in mitochondrial DNA in both DRG neurons and axons. However, this process occurs over a longer time period than a rapidly observed increase in the number of mitochondria in DRG neurites that appears to result, at least in part, from mitochondrial fission. We conclude that during acute hyperglycemia, mitochondrial fission is a prominent response, and excessive mitochondrial fission may result in dysregulation of energy production, activation of caspase 3, and subsequent DRG neuron injury. During more prolonged hyperglycemia, there is evidence of compensatory mitochondrial biogenesis in axons. Our data suggest that an imbalance between mitochondrial biogenesis and fission may play a role in the pathogenesis of diabetic neuropathy.
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影响因子：
3.2
作者：
EL Midaoui, A;Elimadi, A;de Champlain, J
通讯作者：
de Champlain, J
影响因子：
4.4
作者：
Moreira, Paula I.;Santos, Maria S.;Oliveira, Catarina R.
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Oliveira, Catarina R.
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34.7
作者：
Knott, Andrew B.;Perkins, Guy;Schwarzenbacher, Robert;Bossy-Wetzel, Ella
通讯作者：
Bossy-Wetzel, Ella
影响因子：
4.8
作者：
Russell, JW;Golovoy, D;Feldman, EL
通讯作者：
Feldman, EL
影响因子：
3
作者：
Amiri, Mandana;Hollenbeck, Peter J.
通讯作者：
Hollenbeck, Peter J.