S1P 3 receptor influences key physiological properties of fast-twitch extensor digitorum longus muscle
To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P 3 ) in modulating muscle properties, we utilized transgenic mice depleted of the receptor. Morphological analyses of extensor digitorum longus (EDL) muscle did not show evident differences between wild-type and S1P 3 -null mice. Th...
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Veröffentlicht in: | Journal of applied physiology (1985) 2016-06, Vol.120 (11), p.1288-1300 |
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Sprache: | eng |
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Zusammenfassung: | To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P
3
) in modulating muscle properties, we utilized transgenic mice depleted of the receptor. Morphological analyses of extensor digitorum longus (EDL) muscle did not show evident differences between wild-type and S1P
3
-null mice. The body weight of 3-mo-old S1P
3
-null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P
3
deficiency enhanced the expression level of S1P
1
and S1P
2
receptors mRNA in S1P
3
-null EDL muscle. The contractile properties of S1P
3
-null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P
3
appears responsible for a lower availability of calcium during fatigue. S1P supplementation, expected to stimulate residual S1P receptors and signaling, reduced fatigue development of S1P
3
-null muscle. Moreover, in the absence of S1P
3
, denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P
3
-null EDL evidences high levels of the endogenous regulator of mitochondria biogenesis peroxisome proliferative-activated receptor-γ coactivator 1α (PGC-1α); preserving mitochondria could protect the muscle from disuse atrophy. In conclusion, the absence of S1P
3
makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P
3
is involved in the modulation of key physiological properties of the fast-twitch EDL muscle. |
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ISSN: | 8750-7587 1522-1601 |
DOI: | 10.1152/japplphysiol.00345.2015 |