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Exploring pain mechanisms, drug effects and sex dimorphism with proteomics
Author(s) -
Svensson Camilla Ingegerd
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.206.3
Subject(s) - minocycline , microglia , hmgb1 , tlr4 , proteomics , receptor , peptide , medicine , pharmacology , bioinformatics , neuroscience , biology , inflammation , biochemistry , gene , antibiotics
This presentation will give examples of how examining global peptide and protein expression profiles can aid in advancing our understanding of pain mechanisms and effects of pharmacological intervention. Furthermore, the importance of being aware of and understanding the limitations of different extraction methods for peptidomic and proteomics analysis will be highlighted. High‐mobility group box‐1 protein (HMGB1) has emerged as a danger‐associated molecular pattern molecule protein with important roles in various diseases and injury states. Spinal delivery of disulfide HMGB1, which is an endogenous toll like receptor 4 (TLR4) ligand, leads to an increase of factors associated with microglia reactivity in both male and female mice. Interestingly, intrathecal administration of minocycline, frequently used as a microglia inhibitor, attenuated disulfide HMGB1‐induced mechanical hypersensitivity in male but not in female mice. In order to advance our understanding of how HGMB1 induces pain as well as the basis for the sex‐dependent minocycline effect, we examined the global spinal peptide and protein expression profile using LC‐MS/MS. Using a 2×2 factorial design we found that male and females subjected to disulfide HMGB1 show a differential regulation of spinal protein expression. In addition, upon treatment with minocycline there was a striking difference in expression and a statistically significant interaction between gender and the injection effect of minocycline. Thus, the importance of mapping sex‐associated differences in pain mechanisms will be discussed, as well as opportunities and challenges using global protein expression analysis as a basis for such work. Support or Funding Information Swedish Research Council (2013–8373), Knut and Alice Wallenberg Foundation, William K. Bowes Foundation, European Union Seventh Framework Programe (FP7/2007–2013) under grant agreement No. 602919 (GLORIA) and European Union Horizon 2020 research and innovation program under the Marie Sklodowska‐Curie grant agreement No. 642720 (BonePain). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .