title: Analysis of the mitochondrial proteome in multiple sclerosis cortex.
abstract: Mitochondrial dysfunction has been proposed to play a role in the neuropathology of multiple sclerosis (MS). Previously, we reported significant alterations in the transcription of nuclear-encoded electron transport chain genes in MS and confirmed translational alterations for components of Complexes I and III that resulted in reductions in their activity. To more thoroughly and efficiently elucidate potential alterations in the expression of mitochondrial and related proteins, we have characterized the mitochondrial proteome in postmortem MS and control cortex using Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS). Using principal component analysis (PCA) and hierarchical clustering techniques we were able to analyze the differential patterns of SELDI-TOF spectra to reveal clusters of peaks which distinguished MS from control samples. Four proteins in particular were responsible for distinguishing disease from control. Peptide fingerprint mapping unambiguously identified these differentially expressed proteins. Three proteins identified are involved in respiration including cytochrome c oxidase subunit 5b (COX5b), the brain specific isozyme of creatine kinase, and hemoglobin β-chain. The fourth protein identified was myelin basic protein (MBP). We then investigated whether these alterations were consistent in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We found that MBP was similarly altered in EAE but the respiratory proteins were not. These data indicate that while the EAE mouse model may mimic aspects of MS neuropathology which result from inflammatory demyelinating events, there is another distinct mechanism involved in mitochondrial dysfunction in gray matter in MS which is not modeled in EAE.
authors.affiliation: Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44242, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Broadwater
authors.forename: Ashish
authors.initials: A
authors.lastname: Pandit
authors.forename: Robert
authors.initials: R
authors.lastname: Clements
authors.forename: Sausan
authors.initials: S
authors.lastname: Azzam
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vadnal
authors.forename: Michael
authors.initials: M
authors.lastname: Sulak
authors.forename: V Wee
authors.initials: VW
authors.lastname: Yong
authors.forename: Ernest J
authors.initials: EJ
authors.lastname: Freeman
authors.forename: Roger B
authors.initials: RB
authors.lastname: Gregory
authors.forename: Jennifer
authors.initials: J
authors.lastname: McDonough
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000008:administration & dosage; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage; D010449:Peptide Mapping; D025341:Principal Component Analysis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D015415:Biomarkers; D006023:Glycoproteins; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D020543:Proteome; C517781:myelin oligodendrocyte glycoprotein (34-56)