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Involvement of post‐translational modification of neuronal plasticity‐related proteins in hyperalgesia revealed by a proteomic analysis
Author(s) -
Fujisawa Hiroki,
OhtaniKaneko Ritsuko,
Naiki Mitsuru,
Okada Tomoyuki,
Masuko Kayo,
Yudoh Kazuo,
Suematsu Naoya,
Okamoto Kazuki,
Nishioka Kusuki,
Kato Tomohiro
Publication year - 2008
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200700928
Subject(s) - proteome , proteomics , hyperalgesia , quantitative proteomics , biology , cerebellum , neuroscience , central nervous system , microbiology and biotechnology , biochemistry , nociception , receptor , gene
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 p I 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 p I 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.