Hyperglycemia Alters the Schwann Cell Mitochondrial Proteome and Decreases Coupled Respiration in the Absence of Superoxide Production
View/ Open
Issue Date
2010-01Author
Zhang, Liang
Yu, Cuijuan
Vasquez, Francisco Edmundo
Galeva, Nadya
Onyango, Isaac
Swerdlow, Russell Howard
Dobrowsky, Rick T.
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/pr900818g.
Metadata
Show full item recordAbstract
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.
Collections
Citation
Zhang, L., Yu, C., Vasquez, F. E., Galeva, N., Onyango, I., Swerdlow, R. H., & Dobrowsky, R. T. (2010). Hyperglycemia Alters the Schwann Cell Mitochondrial Proteome and Decreases Coupled Respiration in the Absence of Superoxide Production. Journal of Proteome Research, 9(1), 458–471. http://doi.org/10.1021/pr900818g
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.