Increased Post-Translational Lysine Acetylation of Myelin Basic Protein Is Associated with Peak Neurological Disability in a Mouse Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.
J Proteome Res
; 17(1): 55-62, 2018 01 05.
Article
in En
| MEDLINE
| ID: mdl-29111742
ABSTRACT
Citrullination of arginine residues is a post-translational modification (PTM) found on myelin basic protein (MBP), which neutralizes MBPs positive charge, and is implicated in myelin damage and multiple sclerosis (MS). Here we identify lysine acetylation as another neutralizing PTM to MBP that may be involved in myelin damage. We quantify changes in lysine and arginine PTMs on MBP derived from mice induced with an experimental autoimmune encephalomyelitis (EAE) model of MS using liquid chromatography tandem mass spectrometry. The changes in PTMs are correlated to changes in neurological disability scoring (NDS), as a marker of myelin damage. We found that lysine acetylation increased by 2-fold on MBP during peak NDS post-EAE induction. We also found that mono- and dimethyl-lysine, as well as asymmetric dimethyl-arginine residues on MBP were elevated at peak EAE disability. These findings suggest that the acetylation and methylation of lysine on MBP are PTMs associated with the neurological disability produced by EAE. Since histone deacetylase (HDAC) inhibitors have been previously shown to improve neurological disability, we also show that treatment with trichostatin A (a HDAC inhibitor) improves the NDS of EAE mice but does not change MBP acetylation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myelin Basic Protein
/
Encephalomyelitis, Autoimmune, Experimental
/
Lysine
/
Nervous System Diseases
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Proteome Res
Journal subject:
BIOQUIMICA
Year:
2018
Type:
Article
Affiliation country:
Canada