Sirtuin 1 promotes the proliferation of C2C12 myoblast cells via the myostatin signaling pathway

Wang,Liang; Zhang,Ting; Xi,Yongyong; Yang,Cuili; Sun,Chengcao; Li,Dejia

doi:10.3892/mmr.2016.5346

Sirtuin 1 promotes the proliferation of C2C12 myoblast cells via the myostatin signaling pathway

Authors:
- Liang Wang
- Ting Zhang
- Yongyong Xi
- Cuili Yang
- Chengcao Sun
- Dejia Li
View Affiliations

Affiliations: Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: May 27, 2016 https://doi.org/10.3892/mmr.2016.5346
Pages: 1309-1315

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Accumulating evidence suggests that Sirtuin (Sirt)1 serves a significant role in proliferation and differentiation of myoblast cells; however the signaling mechanisms involved remain to be established. Myostatin (MSTN), a member of transforming growth factor‑β family, is an vital regulator of myoblast, fibroblast growth and differentiation. To determine if MSTN is involved in the regulation of myoblast cell proliferation by Sirt1, the present study administrated the Sirt1 activator resveratrol, inhibitor nicotinamide (NAM) and MSTN inhibitor SB431542 to C2C12 myoblast cells. It was demonstrated that the Sirt1 activator, resveratrol, repressed, whereas the Sirt1 inhibitor, NAM, enhanced C2C12 myoblast cells proliferation in a Sirt1‑dependent manner. SB431542 promoted the proliferation of C2C12 myoblast cells and reversed the inhibition effect of NAM on C2C12 myoblast cell proliferation. Additionally, resveratrol upregulated the mRNA expression of MyoD, but inhibited the expression of MSTN. Additionally, NAM significantly repressed the expression of MyoD and the phosphorylation of P107 (p‑P107), but enhanced the expression of MSTN and the protein expression of P107. SB431542 significantly mitigated the effect of NAM on the expression of MyoD, P107 and p‑P107. Taken together, these results indicated that Sirt1 promotes the proliferation of C2C12 myoblast cells via the MSTN signaling pathway.

View Figures

View References

1	Cheng HL, Mostoslavsky R, Saito S, Manis JP, Gu Y, Patel P, Bronson R, Appella E, Alt FW and Chua KF: Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci USA. 100:10794–1099. 2003. View Article : Google Scholar : PubMed/NCBI
2	McBurney MW, Yang X, Jardine K, Hixon M, Boekelheide K, Webb JR, Lansdorp PM and Lemieux M: The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol. 23:38–54. 2003. View Article : Google Scholar :
3	Horio Y, Hayashi T, Kuno A and Kunimoto R: Cellular and molecular effects of sirtuins in health and disease. Clin Sci (Lond). 121:191–203. 2011. View Article : Google Scholar
4	Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, Rengo G, Rossi F and Filippelli A: Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res. 11:139–150. 2008. View Article : Google Scholar
5	Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, et al: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 425:191–196. 2003. View Article : Google Scholar : PubMed/NCBI
6	Jackson MD, Schmidt MT, Oppenheimer NJ and Denu JM: Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases. J Biol Chem. 278:50985–50998. 2003. View Article : Google Scholar : PubMed/NCBI
7	Sauve AA, Moir RD, Schramm VL and Willis IM: Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition. Mol Cell. 17:595–601. 2005. View Article : Google Scholar : PubMed/NCBI
8	Ohanna M, Bonet C, Bille K, Allegra M, Davidson I, Bahadoran P, Lacour JP, Ballotti R and Bertolotto C: SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human melanoma cells. Oncotarget. 5:2085–2095. 2014. View Article : Google Scholar : PubMed/NCBI
9	Mao B, Hu F, Cheng J, Wang P, Xu M, Yuan F, Meng S, Wang Y, Yuan Z and Bi W: SIRT1 regulates YAP2-mediated cell proliferation and chemoresistance in hepatocellular carcinoma. Oncogene. 33:1468–1474. 2014. View Article : Google Scholar
10	Hori YS, Kuno A, Hosoda R, Tanno M, Miura T, Shimamoto K and Horio Y: Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse, a model for duchenne muscular dystrophy. J Pharmacol Exp Ther. 338:784–794. 2011. View Article : Google Scholar : PubMed/NCBI
11	Rathbone CR, Booth FW and Lees SJ: Sirt1 increases skeletal muscle precursor cell proliferation. Eur J Cell Biol. 88:35–44. 2009. View Article : Google Scholar :
12	Tanno M, Sakamoto J, Miura T, Shimamoto K and Horio Y: Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. J Biol Chem. 282:6823–6832. 2007. View Article : Google Scholar : PubMed/NCBI
13	Ripoli M, Barbano R, Balsamo T, Piccoli C, Brunetti V, Coco M, Mazzoccoli G, Vinciguerra M and Pazienza V: Hypermethylated levels of E-cadherin promoter in Huh-7 cells expressing the HCV core protein. Virus Res. 160:74–81. 2011. View Article : Google Scholar : PubMed/NCBI
14	Haigis MC and Sinclair DA: Mammalian sirtuins: Biological insights and disease relevance. Annu Rev Pathol. 5:253–295. 2010. View Article : Google Scholar : PubMed/NCBI
15	Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozaki K, Akishita M, Ouchi Y and Kaneki M: Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene. 25:176–185. 2006.
16	McPherron AC, Lawler AM and Lee SJ: Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 387:83–90. 1997. View Article : Google Scholar : PubMed/NCBI
17	Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J and Kambadur R: Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem. 275:40235–40243. 2000. View Article : Google Scholar : PubMed/NCBI
18	Zhang C, Mcfarlane C, Lokireddy S, Bonala S, Ge X, Masuda S, Gluckman PD, Sharma M and Kambadur R: Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway. Diabetologia. 54:1491–1501. 2011. View Article : Google Scholar : PubMed/NCBI
19	Langley B, Thomas M, Bishop A, Sharma M, Gilmour S and Kambadur R: Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem. 277:49831–49840. 2002. View Article : Google Scholar : PubMed/NCBI
20	Spiller MP, Kambadur R, Jeanplong F, Thomas M, Martyn JK, Bass JJ and Sharma M: The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD. Mol Cell Biol. 22:7066–7082. 2002. View Article : Google Scholar : PubMed/NCBI
21	Ewen ME, Xing YG, Lawrence JB and Livingston DM: Molecular cloning, chromosomal mapping and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell. 66:1155–1164. 1991. View Article : Google Scholar : PubMed/NCBI
22	Hannon GJ, Demetrick D and Beach D: Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev. 7:2378–2391. 1993. View Article : Google Scholar : PubMed/NCBI
23	Mayol X, Graña X, Baldi A, Sang N, Hu Q and Giordano A: Cloning of a new member of the retinoblastoma gene family (pRb2) which binds to the E1A transforming domain. Oncogene. 8:2561–2566. 1993.PubMed/NCBI
24	Assoian RK and Yung Y: A reciprocal relationship between Rb and Skp2: Implications for restriction point control, signal transduction to the cell cycle and cancer. Cell Cycle. 7:24–27. 2008. View Article : Google Scholar : PubMed/NCBI
25	Kabra N, Li Z, Chen L, Li B, Zhang X, Wang C, Yeatman T, Coppola D and Chen J: SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 284:18210–18217. 2009. View Article : Google Scholar : PubMed/NCBI
26	Pardo PS and Boriek AM: The physiological roles of Sirt1 in skeletal muscle. Aging (Albany NY). 3:430–437. 2011. View Article : Google Scholar
27	Olas B and Wachowicz B: Resveratrol, a phenolic antioxidant with effects on blood platelet functions. Platelets. 16:251–260. 2005. View Article : Google Scholar : PubMed/NCBI
28	Banerjee S, Bueso-Ramos C and Aggarwal BB: Suppression of 7,12-dimethylbenz (a)anthracene-induced mammary carcinogenesis in rats by resveratrol: Role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9. Cancer Res. 62:4945–4954. 2002.PubMed/NCBI
29	Lee SJ: Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol. 20:61–86. 2004. View Article : Google Scholar : PubMed/NCBI
30	Taylor WE, Bhasin S, Artaza J, Byhower F, Azam M, Willard DH Jr, Kull FC Jr and Gonzalez-Cadavid N: Myostatin inhibits cell proliferation and protein synthesis in C2C12 muscle cells. Am J Physiol Endocrinol Metab. 280:E221–E228. 2001.PubMed/NCBI
31	Rios R, Carneiro I, Arce VM and Devesa J: Myostatin regulates cell survival during C2C12 myogenesis. Biochem Biophys Res Commun. 280:561–566. 2001. View Article : Google Scholar : PubMed/NCBI
32	Wong S and Weber JD: Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1. Biochem J. 407:451–460. 2007. View Article : Google Scholar : PubMed/NCBI
33	Joulia D, Bernardi H, Garandel V, Rabenoelina F, Vernus B and Cabello G: Mechanisms involved in the inhibition of myoblast proliferation and differentiation by myostatin. Exp Cell Res. 286:263–275. 2003. View Article : Google Scholar : PubMed/NCBI
34	Rathbone CR, Lees SJ and Booth F: Sirt1 increases satellite cell cycle progression. FASEB. 212007.