Suramin affects metalloproteinase-9 activity and increases β-dystroglycan levels in the diaphragm of the dystrophin-deficient mdx mouse.
BACKGROUND
In Duchenne muscular dystrophy and in the mdx mouse, muscle fiber degeneration and subsequent fibrosis lead to cardiorespiratory failure. Previously, we demonstrated that the anti-fibrotic agent suramin was effective in decreasing fibrosis in mdx muscles. In this study, we were interested to see whether suramin could affect metalloproteinases (MMP) and improve the functional activity of the mdx diaphragm muscle.


METHODS
Zymography was performed to evaluate MMP-2 and MMP-9 activity. Western blotting was used to analyze the levels of beta-dystroglycan. Muscle function was assessed in hemidiaphragm in vitro preparations.


RESULTS
We found that suramin affects metalloproteinase-9 activity and increases beta-dystroglycan. Furthermore, suramin also protects against diaphragm muscle fatigue over time.


CONCLUSIONS
These results show the potential benefits of suramin in maintaining the structure of the dystrophin-glycoprotein complex.
Departamento de Anatomia, Biologia Celular, Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo 13083-970, Brazil.
Ana Paula Tiemi
AP
Taniguti
Cíntia Yuri
CY
Matsumura
Léa
L
Rodrigues-Simioni
Humberto
H
Santo Neto
Maria Julia
MJ
Marques
D000818:Animals; D003964:Diaphragm / Q000187:drug effects / Q000378:metabolism*; D049030:Dystroglycans / Q000096:biosynthesis / Q000378:metabolism*; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005355:Fibrosis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D013498:Suramin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016189:Dystrophin; D061965:Matrix Metalloproteinase Inhibitors; D049030:Dystroglycans; D013498:Suramin; D020780:Matrix Metalloproteinase 9