Hyperglycemia alters the schwann cell mitochondrial proteome and decreases coupled respiration in the absence of superoxide production.
Hyperglycemia alters the schwann cell mitochondrial proteome and decreases coupled respiration in the absence of superoxide production.
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DOI：
10.1021/pr900818g
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发表时间：
2010-01
影响因子：
4.4
通讯作者：
Dobrowsky, Rick T.
中科院分区：
文献类型：
--
作者：
Zhang, Liang;Yu, Cuijuan;Vasquez, Francisco E.;Galeva, Nadya;Onyango, Isaac;Swerdlow, Russell H.;Dobrowsky, Rick T.
高血糖诱导的线粒体功能障碍导致糖尿病神经病变的感觉神经元病理学。虽然雪旺细胞（SC）在糖尿病神经病变中也发生了实质性的变性，但高血糖对SC线粒体蛋白质组和线粒体功能的影响尚未得到研究。使用细胞培养物中的氨基酸稳定同位素标记（SILAC）来量化高血糖对从新生大鼠分离的原代SC的线粒体蛋白质组的时间效应。在鉴定的317种线粒体蛋白中，约78%在多个时间点被定量和检测。通路分析表明，与线粒体功能障碍，氧化磷酸化，TCA循环和解毒相关的蛋白质的表达显着增加和过度代表。评估完整的SC中的线粒体呼吸表明，高血糖增加了总的耗氧率，但降低了耦合呼吸的效率。虽然葡萄糖依赖性增加超氧化物的产生发生在胚胎感觉神经元，高血糖症并没有引起超氧化物水平的SC的实质性变化。这与锰超氧化物歧化酶的表达增加了1.9倍，这是通过免疫印迹和酶活性测定证实。这些数据支持高血糖改变线粒体呼吸，并可导致SC线粒体蛋白质组的重塑，而不依赖于葡萄糖诱导的超氧化物产生的显著贡献。
Hyperglycemia-induced mitochondrial dysfunction contributes to sensory neuron pathology in diabetic neuropathy. Although Schwann cells (SCs) also undergo substantial degeneration in diabetic neuropathy, the effect of hyperglycemia on SC mitochondrial proteome and mitochondrial function has not been examined. Stable isotope labeling with amino acids in cell culture (SILAC) was used to quantify the temporal effect of hyperglycemia on the mitochondrial proteome of primary SCs isolated from neonatal rats. Of 317 mitochondrial proteins identified, about 78% were quantified and detected at multiple time points. Pathway analysis indicated that proteins associated with mitochondrial dysfunction, oxidative phosphorylation, the TCA cycle and detoxification were significantly increased in expression and over-represented. Assessing mitochondrial respiration in intact SCs indicated that hyperglycemia increased the overall rate of oxygen consumption but decreased the efficiency of coupled respiration. Although a glucose-dependent increase in superoxide production occurs in embryonic sensory neurons, hyperglycemia did not induce a substantial change in superoxide levels in SCs. This correlated with a 1.9 fold increase in Mn superoxide dismutase expression which was confirmed by immunoblot and enzymatic activity assays. These data support that hyperglycemia alters mitochondrial respiration and can cause remodeling of the SC mitochondrial proteome independent of significant contributions from glucose-induced superoxide production.
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影响因子：
7
作者：
Hwang, Sun-Il;Lundgren, Deborah H.;Han, David K.
通讯作者：
Han, David K.
影响因子：
7.7
作者：
Ho, Eric C. M.;Lam, Karen S. L.;Chung, Sookja K.
通讯作者：
Chung, Sookja K.
影响因子：
46.9
作者：
Blagoev, B;Ong, SE;Mann, M
通讯作者：
Mann, M
哺乳动物线粒体蛋白质组的组织异质性
影响因子：
5.5
作者：
Johnson, D. Thor;Harris, Robert A.;Balaban, Robert S.
通讯作者：
Balaban, Robert S.
DOI：
10.1016/s0169-328x(01)00009-2
发表时间：
2001-03-05
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Maekawa, K;Tanimoto, T;Yabe-Nishimura, C
通讯作者：
Yabe-Nishimura, C