Article (Scientific journals)
Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy
Gilson, H.; Schakman, O.; Combaret, L. et al.
2007In Endocrinology, 148 (1), p. 452-460
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Abstract :
[en] Glucocorticoids mediate muscle atrophy in many catabolic states. Myostatin expression, a negative regulator of muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent muscle atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for 10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in muscle atrophy (tibialis anterior: -15%; gastrocnemius: -13%; P < 0.01) due to 15% decrease in the muscle fiber cross-sectional area (1621 +/- 31 vs. 1918 +/- 64 mu m(2), P < 0.01). In KO mice, there was no reduction of muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle atrophy after 4d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents muscle atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in muscle atrophy caused by glucocorticoids.
Disciplines :
Genetics & genetic processes
Endocrinology, metabolism & nutrition
Author, co-author :
Gilson, H.;  Université Catholique de Louvain - UCL > Unité de Diabétologie et Nutrition
Schakman, O.;  Université Catholique de Louvain - UCL > Unité de Diabétologie et Nutrition
Combaret, L.;  Institut National de la Recherche Agronomique - INRA > Human Nutrition Research Centre of Clermont-Ferrand > Human Nutrition Unit
Lause, P.;  Université Catholique de Louvain - UCL > Unité de Diabétologie et Nutrition
Grobet, Luc ;  Université de Liège - ULiège > Département de morphologie et pathologie > Embryologie
Attaix, D.;  Institut National de la Recherche Agronomique - INRA > Human Nutrition Research Centre of Clermont-Ferrand > Human Nutrition Unit
Ketelslegers, J. M.;  Université Catholique de Louvain - UCL > Unité de Diabétologie et Nutrition
Thissen, J. P.;  Université Catholique de Louvain - UCL > Unité de Diabétologie et Nutrition
Language :
English
Title :
Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy
Publication date :
January 2007
Journal title :
Endocrinology
ISSN :
0013-7227
eISSN :
1945-7170
Publisher :
Endocrine Soc, Chevy Chase, United States - Maryland
Volume :
148
Issue :
1
Pages :
452-460
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 June 2011

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