title: S1P3 receptor influences key physiological properties of fast-twitch extensor digitorum longus muscle.
abstract: To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P3) 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 S1P3-null mice. The body weight of 3-mo-old S1P3-null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P3 deficiency enhanced the expression level of S1P1 and S1P2 receptors mRNA in S1P3-null EDL muscle. The contractile properties of S1P3-null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P3 appears responsible for a lower availability of calcium during fatigue. S1P supplementation, expected to stimulate residual S1P receptors and signaling, reduced fatigue development of S1P3-null muscle. Moreover, in the absence of S1P3, denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P3-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 S1P3 makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P3 is involved in the modulation of key physiological properties of the fast-twitch EDL muscle.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy; IIM, Interuniversity Institute of Myology, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy;
authors.forename: Michela
authors.initials: M
authors.lastname: Bondì
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Biomedical, Experimental and Clinical Sciences, Mario Serio, University of Firenze, Florence, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Cencetti
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Biomedical, Experimental and Clinical Sciences, Mario Serio, University of Firenze, Florence, Italy;
authors.forename: Chiara
authors.initials: C
authors.lastname: Donati
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy;
authors.forename: Marta
authors.initials: M
authors.lastname: Nocella
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy;
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0003-1397-9791
authors.initials: B
authors.lastname: Colombini
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; CNR-Institute for Neuroscience, CNR, Padova, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Biomedical, Experimental and Clinical Sciences, Mario Serio, University of Firenze, Florence, Italy;
authors.forename: Paola
authors.initials: P
authors.lastname: Bruni
authors.affiliation: IIM, Interuniversity Institute of Myology, Italy; Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy;
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Bagni
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy; IIM, Interuniversity Institute of Myology, Italy; daniela.danieli@unipd.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli-Betto
mesh_terms: D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000378:metabolism / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000502:physiology*; D009135:Muscular Diseases / Q000378:metabolism / Q000503:physiopathology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D049349:Receptors, Lysosphingolipid; C501285:S1pr3 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; D002118:Calcium
keywords: atrophy; contractile properties; fast muscle; fatigue; sphingosine 1-phosphate; sphingosine 1-phosphate receptor 3