Okadaic acid augments utrophin in myogenic cells
Neuroscience Letters, 2004
Marianna Rodova, Kyle Brownback, Michael J. Werle –
USA
Abstract :
Duchenne
muscular dystrophy is a fatal childhood disease caused by mutations that
abolish the expression of dystrophin in muscle. Utrophin is a paralogue of
dystrophin and can functionally replace it in skeletal muscle. A potential
therapeutic approach is to increase utrophin levels in muscle. One way to
achieve this aim is to increase the expression of the utrophin gene at a
transcriptional level via promoter activation. In this study, we have shown
that utrophin A mRNA levels can be induced by okadaic acid in murine myogenic
C2C12 cells. We have found that a utrophin A promoter reporter can be induced
by Sp1 in C2C12 myoblasts, but not in myotubes. This activation can be enhanced
by okadaic acid treatment. Our data suggest that this induction is due to Sp1
phosphorylation during myogenesis and thus, utrophin expression in muscle could
be regulated by treatment with phosphatase inhibitors. Control of utrophin
promoter activation could then be used to increase the expression of utrophin,
and thus ameliorate the symptoms of Duchenne muscular dystrophy.