ANTAGONISTS
Loss of skeletal muscle mass and strength is a central feature of
traumatic injuries and degenerative myopathies. Unfortunately,
pharmacological interventions often fail to stem the long-term decline
in quality of life. REV-ERB-mediated reduced gene suppression in
cultured c2c12 myoblasts has been shown to stimulate myoblast
differentiation. However, the mechanisms that allow REV-ERB to
pleiotropically inhibit muscle differentiation are not well known. Thus,
a study elucidated the role of REV-ERB in regulating muscle
differentiation and regeneration in vivo. The REV-ERB α/β
regulation mechanism for muscle differentiation and regeneration was
analyzed. Myoblast analysis showed that REV-ERB α did not
transcriptionally regulate muscle differentiation through cognate
elements REV-ERB/ror-response, but through a possible interaction with
the regulator of nf-y cell fate in ccaat motifs. Muscle differentiation
is stimulated by the release of REV-ERB from CCAAT motifs in the
elements promoting and enhancing various myogenic proteins. Therefore,
the interruption of REV-ERB activity in the injured muscle accelerates
regenerative muscle repair/differentiation through the transcriptional
detoxification of myogenic programs. Thus, REV-ERB can be a potent
therapeutic target for a multitude of muscle disorders [57].
In previous investigations, we have reported that activation of the β/δ
receptor activated by the peroxisome proliferator by gw501516 inhibits
proliferation and promotes apoptosis in the undifferentiated cells of
c666-1 nasopharyngeal carcinoma (NPC) modulating the caspase-dependent
apoptotic pathway. Thus, a study explored the mechanism by which
gw501516 induces apoptosis through the expression of the microwave
(mirna). Among the mirnas analyzed involved in regulating the expression
of the anti-apoptotic protein bcl-2, mir-206 increased significantly and
specifically by gw501516 in c666-1 cells, both in vitro and in xenograft
samples in vivo . The induction in mir-206 expression caused by
gw501516 was able to be antagonized by the antagonist gsk3787 of pparβ/δ
and by the dorsomorphine antagonist of ampk in cells c666-1. Suppression
of gw501516 in the growth and apoptosis of c666-1 cells has been found
to depend on the presence of mir-206 [58].
The overexpression of mir-206 resulted in suppressed proliferation and
the ability to form colonies, in addition to triggering increased
apoptosis in c666-1 cells in a caspase-dependent manner. the expression
of cleaved caspase 3 and caspase 9, and the ratio of bax to bcl-2 were
increased notably by mir-206. Current data has shown that mir-206 plays
a critical role in the direct promotion effect of gw501516-induced
apoptosis in c666-1 cells. Also, the emphasized tumor-suppressing role
of mir-206 in c666-1 cells indicates that it has the potential to
provide a new therapeutic approach [58].