title: Hyperglycemia alters the schwann cell mitochondrial proteome and decreases coupled respiration in the absence of superoxide production.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology and Analytic Proteomics Laboratory, University of Kansas, Lawrence, Kansas 66045, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Yu
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Vasquez
authors.forename: Nadya
authors.initials: N
authors.lastname: Galeva
authors.forename: Isaac
authors.initials: I
authors.lastname: Onyango
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: Rick T
authors.initials: RT
authors.lastname: Dobrowsky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D007553:Isotope Labeling; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010100:Oxygen; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome; D013481:Superoxides; D013482:Superoxide Dismutase; D010100:Oxygen