title: Proteomics and neuromuscular diseases: theoretical concept and first results.
abstract: Although many patients suspected of suffering disturbances of the mitochondrial energy metabolism have been investigated, only a fraction of these patients have been diagnosed at the molecular level. Introduction of new techniques like proteomics will be necessary to understand the various clinical and biochemical aberrations in the field of mitochondrial disorders. Two-dimensional electrophoresis is the first, important step in the proteomics strategy. Separation of soluble proteins is performed on the basis of isoelectric point (net charge) in one direction and on molecular mass in the other. The technique provides an overview of the majority of proteins expressed in a sample (e.g. muscle biopsy, muscle cell or mitochondrial fraction). Once an abnormal spot is observed in the gel the responsible protein can be identified by analysing a limited part of its amino acid sequence by mass spectrometry. We optimized two-dimensional (2D) gel electrophoresis to obtain high resolution 2D-maps and tested the reproducibility of the technique. Potentially, this new technique is capable of identifying novel mitochondrial diseases and defining their molecular basis.
authors.affiliation: University Medical Center Nijmegen, Laboratory for Pediatrics and Neurology, Department of Pediatrics, Geert Grooteplein 20, 6500 HB Nijmegen, The Netherlands. b.vandenheuvel@cukz.umcn.nl
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: M H
authors.initials: MH
authors.lastname: Farhoud
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
authors.forename: B G M
authors.initials: BG
authors.lastname: van Engelen
authors.forename: J A M
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D008928:Mitochondria / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000378:metabolism*; D009468:Neuromuscular Diseases / Q000175:diagnosis / Q000378:metabolism*; D020543:Proteome
chemical_list: D020543:Proteome