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29.4
Discussion
In the present study, the differentiation of C2C12 fibroblast to myotube was
significantly and dose-dependently enhanced by taurine treatment, and the effect
of taurine was abrogated by the inhibitions of Ca
2+
, its signaling pathway, and
endogenous taurine transport. Myogenesis consists of multiple processes includ-
ing ceasing of proliferation, elongation, and fusion into multinucleated myotube,
and many factors including insulin growth factor 1 and myocyte-enhanced factor
2 have been reported to enhance these processes in the previous studies (Gossett
et al.
1989
; Kook et al.
2008
; Maeda et al.
2002
; Naya and Olson
1999
; Semsarian
et al.
1999
). Taurine might be one of the important factors that regulate muscle
maturation in the development period. In the processes of muscle hypertrophy
including the fusion of myoblast and the formation of myotube, extracellular
Ca
2+
and Ca
2+
-dependent calcineurin (Ca
2+
/calmodulin-dependent phosphatase)
signaling are important pathways (De Arcangelis et al.
2005
; Semsarian et al.
1999
). In the present study, the enhanced effects of taurine on the differentiation
of C2C12 cells were cancelled by treatments of Ca
2+
chelator nifedipine and cal-
cineurin inhibitor FK-506, and these results supported the role of taurine on the
Ca
2+
-calcineurin pathway in the differentiation process. The enhanced mRNA
expression of MCIP1 by nifedipine treatment was significantly decreased by tau-
rine treatment. The MCIP1 expresses primarily in skeletal muscle and inhibits
the activity of calcineurin (Rothermel et al.
2000
). Because the gene transcrip-
tion is potently stimulated by activated calcineurin as negative feedback (Yang
et al.
2000
), it is possible that taurine might suppress the feedback transcription
of MCIP1. Furthermore, it is suggested that intracellular, but not external, tau-
rine uptaken from culture medium might affect on the pathway because the tau-
rine transport inhibitor b-alanine treatment and taut gene silencing significantly
inhibited the cell differentiation.
29.5
Conclusion
In summary, the present study shows that exogenous taurine treatment
significantly enhanced the differentiation of C2C12 myoblast to myotube, and
the significant effect of taurine might be associated with the Ca
2+
signaling path-
way. This beneficial effect of taurine would possibly contribute to the muscle
recovery after damages.
Acknowledgements
This work was supported in part by Kakenhi grants (21790633) from the
Japan Society for the Promotion of Science.
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