Skeletal Muscle Differentiation: Role of Dehydroepiandrosterone Sulfate

R. Ceci; G. Duranti; A. Rossi; I. Savini; S. Sabatini

doi:10.1055/s-0031-1285867

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2011; 43(10): 702-707
DOI: 10.1055/s-0031-1285867

Original Basic

Georg Thieme Verlag KG Stuttgart · New York

Skeletal Muscle Differentiation: Role of Dehydroepiandrosterone Sulfate

Authors

R. Ceci^§

¹Department of Health Sciences, University of Rome “Foro Italico”, Rome, Italy
G. Duranti^§

¹Department of Health Sciences, University of Rome “Foro Italico”, Rome, Italy
A. Rossi

²Department of Experimental Medicine & Biochemical Sciences, University of Rome “Tor Vergata”, Rome, Italy
I. Savini

²Department of Experimental Medicine & Biochemical Sciences, University of Rome “Tor Vergata”, Rome, Italy
S. Sabatini

¹Department of Health Sciences, University of Rome “Foro Italico”, Rome, Italy

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.

Key words

DHEAS - C2C12 differentiation - MuRF-1 - myosin heavy chain - heat shock proteins

Full Text

References

References
1 Bassel-Duby R, Olson EN. Signaling pathways in skeletal muscle remodeling. Annu Rev Biochem 2006; 75: 19-37
2 Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M, Mauras N, Bowers CY. Endocrine control of body composition in infancy, childhood and puberty. Endocr Rev 2005; 26: 114-146
3 Glass DJ. Molecular mechanism modulating muscle mass. Trends Mol Med 2003; 9: 344-350
4 Faulkner JA, Brooks SV, Zerba E. Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. J Gerontol A Biol Sci Med Sci 1995; A50: 124-129
5 Baulieu EE. Dehydroepiandrosterone (DHEA): a fountain of youth?. J Clin Endocrinol Metab 1996; 81: 3147-3151
6 Yen SS. Dehydroepiandrosterone sulphate and longevity: new clues for an old friend. Proc Natl Acad Sci USA 2001; 98: 8167-8168
7 Hornsby PJ. Biosynthesis of DHEAS by the human adrenal cortex and its age-related decline. Ann NY Acad Sci 1995; 774: 29-46
8 Hughes VA, Frontera WR, Roubenoff R, Evans WJ, Singh MA. Longitudinal changes in body composition in older men and women: role of body weight change and physical activity. Am J Clin Nutr 2002; 76: 473-481
9 Perry RI, Rudnick MA. Molecular mechanism regulating myogenic determination and regeneration. Front Biosci 2000; 5: D750-D767
10 Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ. Identification of ubiquitin ligases required for muscle atrophy. Science 2001; 294: 1704-1708
11 Murton AJ, Costantin D, Greenhaff PL. The involvement of the ubiquitin proteasome system in human skeletal muscle remodeling and atrophy. Biochem Biophys Acta 2008; 1782: 730-743
12 Clarke BA, Drujan D, Willis MS, Murphy LO, Corpina RA, Burova E, Rakhilin SV, Stitt TN, Patterson C, Latre E, Glass DJ. The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle. Cell Metab 2007; 6: 376-385
13 Richter K, Haslbeck M, Buchner J. The heat shock response: life on the verge of death. Mol Cell 2010; 40: 253-266
14 Senf SM, Dodd SL, McClung MJ, Judge AR. Hsp70 overexpression inhibits NF-κB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J 2008; 22: 3836-3845
15 Dodd SL, Hain B, Senf SM, Judge AR. Hsp27 inhibits IKKbeta-induced NF-kappaB activity and skeletal muscle atrophy. FASEB J 2009; 23: 3415-3423
16 Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and it is directly regulated by Hsp 70. Am J Physiol Cell Physiol 2010; 298: C38-C45
17 McArdle A, Broome CS, Kayani AC, Tully MD, Close GL, Vasilaki A, Jackson MJ. HSF expression in skeletal muscle during myogenesis: Implications for failed regeneration in old mice. Exp Gerontol 2006; 41: 497-500
18 Vasilaki A, Jackson MJ, McArdle A. Attenuated HSP70 response in skeletal muscle of aged rats following contractile activity. Muscle Nerve 2002; 25: 902-905
19 Stevenson EJ, Giresi PG, Koncarevic A, Kandarian SC. Global analysis of gene expression patterns during disuse atrophy in rat skeletal muscle. J Physiol 2003; 551: 33-48
20 Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, Price SR, Mitch WE, Goldberg AL. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 2004; 18: 39-51
21 Voznesensky M, Walsh S, Dauser D, Brindisi J, Kenny AM. The association between dehydroepiandrosterone and frailty in older men and women. Age Ageing 2009; 38: 401-406
22 Yaffe D, Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature 1977; 279: 725-727
23 Catani MV, Savini I, Duranti G, Caporossi D, Ceci R, Sabatini S, Avigliano L. Nuclear factor kappaB and activating protein 1 are involved in differentiation-related resistance to oxidative stress in skeletal muscle cells. Free Radic Biol Med 2004; 37: 1024-1036
24 Chulman J, Inho J, Insun C, Sung-Chul J, Joon K, Sung SK, Sangmee AJ. Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells by activating ERK. Biochim Biophys Acta 2005; 1743: 187-197
25 McArdle A, Dillmann WH, Mestril R, Faulkner JA, Jackson MJ. Over-expression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction. FASEB J 2004; 18: 355-357
26 Radford DJ, Wang K, McNelis JC, Taylor AE, Hechenberg G, Hofmann J, Chahal H, Arlt W, Lord JM. Dehydroepiandrosterone Sulfate directly activates protein kinase C-β to increase human neutrophil superoxide generation. Mol Endocrinol 2010; 24: 813-821
27 Ziegler CG, Langbein H, Krug AW, Ludwig B, Eisenhofer G, Ehrhart-Bornstein M, Bornstein SR. Direct effect of dehydroepiandrosterone sulfate (DHEAS) on PC12 cell differentiation processes. Mol Cell Endocrinol 2011; 336: 149-155
28 Hernández-García D, Wood CD, Castro-Obregón S, Covarrubias L. Reactive oxygen species: A radical role in development?. Free Radic Biol Med 2010; 49: 130-143
29 Su B, Mitra S, Gregg H, Flavahan S, Chotani MA, Clark KR, Goldschmidt-Clermont PJ, Flavahan NA. Redox regulation of vascular smooth muscle cell differentiation. Circ Res 2001; 89: 39-46
30 Hansen JM, Klass M, Harris C, Csete M. A reducing redox environment promotes C2C12 myogenesis. Implications for regeneration in aged muscle. Cell Biol Int 2007; 31: 546-553
31 Li YP, Chen Y, Li AS, Reid MB. Hydrogen peroxide stimulates ubiquitin-conjugating activity and expression of genes for specific E2 and E3 proteins in skeletal muscle myotubes. Am J Pysiol Cell Pysiol 2003; 285 (4): C806-C812
32 Luu-The V, Labrie F. The intracrine sex steroid biosynthesis pathways. Prog Brain Res 2010; 181: 177-192
33 Pires-Oliveira M, Maragno AL, Parreiras-e-Silva LT, Chiavegatti T, Gomes MD, Godinho RO. Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo. J Appl Physiol 2010; 108: 266-273
34 Luu-The V, Dufort I, Paquet N, Reimnitz G, Labrie F. Structural characterization and expression of the human dehydroepiandrosterone sulfotransferase gene. DNA Cell Biol 1995; 14: 511-518
35 Aizawa K, Iemitsu M, Maeda S, Subrina J, Otsuki T, Mowa CN, Miyauchi T, Mesaki N. Expression of steroidogenic enzymes and synthesis of sex steroid hormones from DHEA in skeletal muscle of rats. Am J Physiol Endocrinol Metab 2007; 292: E577-E584
36 Tsuji K, Furutama D, Tagami M, Ohsawa N. Specific binding and effects of dehydroepiandrosterone sulphate (DHEA-S) on skeletal muscle cells: possible implication for DHEA-S replacement therapy in patients with myotonic dystrophy. Life Sci 1999; 65: 17-26
37 Sacheck JM, Ohtsuka A, McLary C, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab 2004; 287: E591-E601