title: Involvement of post-translational modification of neuronal plasticity-related proteins in hyperalgesia revealed by a proteomic analysis.
abstract: To clarify roles of an endogenous pain modulatory system of the central nervous system (CNS) in hyperalgesia, we tried to identify qualitative and quantitative protein changes by a proteomic analysis using an animal model of hyperalgesia. Specifically, we first induced functional hyperalgesia on male Wistar rats by repeated cold stress (specific alternation of rhythm in temperature, SART). We then compared proteomes of multiple regions of CNS and the dorsal root ganglion between the hyperalgetic rats and non-treated ones by 2-D PAGE in the pI range of 4.0-7.0. We found that SART changed the proteomes prominently in the mesencephalon and cerebellum. We thus analyzed the two brain regions in more detail using gels with narrower pI ranges. As a result, 29 and 23 protein spots were significantly changed in the mesencephalon and the cerebellum, respectively. We successfully identified 12 protein spots by a MALDI-TOF/TOF MS and subsequent protein database searching. They included unc-18 protein homolog 67K, collapsin response mediator protein (CRMP)-2 and CRMP-4, which were reported to be involved in neurotransmitter release or axon elongation. Interestingly, mRNA expression levels of these three proteins were not changed significantly by the induction of hyperalgesia. Instead, we found that the detected changes in the protein spots are caused by the post-translational modification (PTM) of proteolysis or phosphorylation. Taken together, development of the hyperalgesia would be linked to PTM of these three CNS proteins. PTM regulation may be one of the useful ways to treat hyperalgesia.
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Ohtani-Kaneko
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Naiki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okada
authors.forename: Kayo
authors.initials: K
authors.lastname: Masuko
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yudoh
authors.forename: Naoya
authors.initials: N
authors.lastname: Suematsu
authors.forename: Kazuki
authors.initials: K
authors.lastname: Okamoto
authors.forename: Kusuki
authors.initials: K
authors.lastname: Nishioka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003080:Cold Temperature / Q000009:adverse effects; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008465:Mechanoreceptors / Q000378:metabolism; D051938:Munc18 Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000032:analysis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017931:DNA Primers; C449760:Dpysl3 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D020543:Proteome; D012333:RNA, Messenger; C095114:collapsin response mediator protein-2