title: Skeletal muscle differentiation: role of dehydroepiandrosterone sulfate.
abstract: Dehydroepiandrosterone (DHEA) and its sulfonated form dehydroepiandrosterone sulfate (DHEAS) are the main circulating steroid hormones and many epidemiological studies show an inverse relationship between DHEA/DHEAS levels and muscle loss for which the primary cause is the accelerated protein breakdown. The aim of this work was to determine whether DHEA/DHEAS supplementation in differentiating C2C12 skeletal muscle cells might influence the expression of the atrophy-related ubiquitin ligase, MuRF-1, and thereby impact key molecules of the differentiation program. DHEA is the prohormone crucial for sex steroid synthesis, and DHEAS is thought to be its reservoir. However, our preliminary experiments showed that DHEAS, but not DHEA, is able to influence MuRF-1 expression. Therefore, we treated differentiating C2C12 cells with various concentrations of DHEAS and analyzed the expression of MuRF-1, Hsp70, myosin heavy chain (MHC), myogenin, and the activity of creatine kinase. We observed that DHEAS at physiological concentrations downregulates MuRF-1 expression and affects muscle differentiation, as shown by the increased levels of MHC, which is a sarcomeric protein that undergoes MuRF-1-dependent degradation, and also by an increase in creatine kinase activity and myogenin expression, which are two other well-known markers of differentiation. Moreover, we found that DHEAS might have a protective effect on differentiating cells as suggested by the augmented levels of Hsp70, a member of heat shock proteins family that, besides its cytoprotective action, seems to have a regulatory role on key atrophy genes such as MuRF-1. In conclusion, our data shed light on the role of DHEAS at physiologic concentrations in maintaining muscle mass.
authors.affiliation: Department of Health Sciences, University of Rome Foro Italico, Rome, Italy. roberta.ceci@uniroma4.it
authors.forename: R
authors.initials: R
authors.lastname: Ceci
authors.forename: G
authors.initials: G
authors.lastname: Duranti
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: I
authors.initials: I
authors.lastname: Savini
authors.forename: S
authors.initials: S
authors.lastname: Sabatini
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology*; D018008:Myogenin / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D009124:Muscle Proteins; D018008:Myogenin; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; D019314:Dehydroepiandrosterone Sulfate; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D003402:Creatine Kinase; D018995:Myosin Heavy Chains