Hyperglycemia Alters the Schwann Cell Mitochondrial Proteome and Decreases Coupled Respiration in the Absence of Superoxide Production

被引:52
|
作者
Zhang, Liang [1 ]
Yu, Cuijuan [1 ]
Vasquez, Francisco E. [1 ]
Galeva, Nadya
Onyango, Isaac [2 ]
Swerdlow, Russell H. [2 ]
Dobrowsky, Rick T. [1 ]
机构
[1] Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA
[2] Univ Kansas, Dept Mol & Integrat Physiol, Med Ctr, Kansas City, KS 66160 USA
基金
美国国家卫生研究院;
关键词
diabetes; hyperglycemia; SILAC; Schwann cells; mitochondria; superoxide dismutase; oxidative stress; POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; STREPTOZOTOCIN-DIABETIC RATS; OXIDATIVE-NITROSATIVE STRESS; ALDOSE REDUCTASE; SENSORY NEURONS; HIGH-GLUCOSE; UNCOUPLING PROTEINS; CULTURE SILAC; AMINO-ACIDS; NEUROPATHY;
D O I
10.1021/pr900818g
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 the 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.
引用
收藏
页码:458 / 471
页数:14
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