S1P^sub 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^sub 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^sub 3^-null...

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Bibliographic Details
Published in:	Journal of applied physiology (1985) 2016-06, Vol.120 (11), p.1288
Main Authors:	Germinario, Elena, Bondì, Michela, Cencetti, Francesca, Donati, Chiara, Nocella, Marta, Colombini, Barbara, Betto, Romeo, Bruni, Paola, Bagni, Maria Angela, Danieli-Betto, Daniela
Format:	Article
Language:	eng
Subjects:	Gene expression Muscular system Protein expression Rodents
Online Access:	Get full text
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Summary:	To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P^sub 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^sub 3^-null mice. The body weight of 3-mo-old S1P^sub 3^-null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P^sub 3^ deficiency enhanced the expression level of S1P^sub 1^ and S1P^sub 2^ receptors mRNA in S1P^sub 3^-null EDL muscle. The contractile properties of S1P^sub 3^-null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P^sub 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^sub 3^-null muscle. Moreover, in the absence of S1P^sub 3^, denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P^sub 3^-null EDL evidences high levels of the endogenous regulator of mitochondria biogenesis peroxisome proliferative-activated receptor-y coactivator 1α (PGC-1α); preserving mitochondria could protect the muscle from disuse atrophy. In conclusion, the absence of S1P^sub 3^ makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P^sub 3^ is involved in the modulation of key physiological properties of the fast-twitch EDL muscle.
ISSN:	8750-7587 1522-1601