Proteomic profile of differentially expressed plasma proteins from dystrophic mice and following suberoylanilide hydroxamic acid treatment.
OBJECTIVE
Histone Deacetylase Inhibitors (DI) ameliorates dystrophic muscle regeneration restoring muscular strength in the mdx mouse model of Duchenne muscular dystrophy (DMD). The further development of these compounds as drugs for DMD treatment is currently hampered by the lack of knowledge about DIs effect in large dystrophic animal models and that of suitable biomarkers to monitor their efficacy.


METHODS
In this study we applied proteomic analysis to identify differentially expressed proteins present in plasma samples from mdx mice treated with the Suberoylanilide hydroxamic acid (SAHA) and relative normal controls (WT).


RESULTS
Several differentially expressed proteins were identified between untreated wild type and mdx mice. Among these, fibrinogen, epidermal growth factor 2 receptor, major urinary protein and glutathione peroxidase 3 (GPX3) were constitutively up-regulated in mdx, while complement C3, complement C6, gelsolin, leukaemia inhibitory factor receptor (LIFr), and alpha 2 macroglobulin were down-regulated compared to WT mice. SAHA determined the normalization of LIFr and GPX3 protein level while apoliprotein E was de novo up-regulated in comparison to vehicle-treated mdx mice.


CONCLUSIONS
Collectively, these data unravel potential serological disease biomarkers of mdx that could be useful to monitor muscular dystrophy response to DI treatment.
Centro Cardiologico Monzino-IRCCS, Milano, Italy.
C
C
Colussi
C
C
Banfi
M
M
Brioschi
E
E
Tremoli
S
S
Straino
F
F
Spallotta
Antonello
A
Mai
Dante
D
Rotili
M C
MC
Capogrossi
Carlo
C
Gaetano
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008969:Molecular Sequence Data; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D020543:Proteome / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D000077337:Vorinostat
D001798:Blood Proteins; D006877:Hydroxamic Acids; D020543:Proteome; D000077337:Vorinostat