Skip to main content

Advertisement

Log in

The environmental pollutant cadmium induces homeostasis alteration in muscle cells in vitro

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background

Cadmium (Cd) is a heavy metal widely distributed throughout the environment as a result of contamination from a variety of sources. It exerts toxic effects in many tissues but scarce data are present as yet on potential effects on skeletal muscle tissue.

Aim

To evaluate the potential alteration induced by Cd in skeletal muscle cells.

Materials and methods

C2C12 skeletal muscle cells were treated with Cd at different times of cellular differentiation and gene expression was evaluated.

Results

Exposure to Cd decreased significantly p21 mRNA expression and strongly up-regulated cyclin D1 mRNA expression in committed cells and in differentiated myotubes. Moreover, myogenin, fast MyHC-IIb and slow MyHC-I mRNAs expression were also significantly decreased both in committed cells and in myotubes. Moreover, Cd exposure induced a strong increase of Pax3, Pax7 and Myf5 mRNAs expression and stimulated an up-regulation of IL6 and TNF-α proinflammatory cytokines.

Conclusion

These data lead to hypothesize that environmental Cd exposure might trigger an injury-like event in muscle tissue, possibly by an estrogen receptor-mediated mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

Cd:

Cadmium

CdCl2 :

Cadmium chloride

MyHC:

Myosin heavy chain

References

  1. Järup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238:201–208

    Article  PubMed  Google Scholar 

  2. Nawrot TS, Staessen JA, Roels HA et al (2010) Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 23:769–782

    Article  PubMed  CAS  Google Scholar 

  3. Bernhoft RA (2013) Cadmium toxicity and treatment. Sci World J

  4. Beyersmann D, Hechtenberg S (1997) Cadmium, gene regulation, and cellular signaling in mammalian cells. Toxicol Appl Pharmacol 144:247–261

    Article  PubMed  CAS  Google Scholar 

  5. Zheng H, Liu J, Choo KH et al (1996) Metallothionein-I and -II knock-out mice are sensitive to cadmium-induced liver mRNA expression of c-jun and p53. Toxicol Appl Pharmacol 136:229–235

    Article  PubMed  CAS  Google Scholar 

  6. Dormer UH, Westwater J, McLaren NF et al (2000) Cadmium-inducible expression of the yeast GSH1 gene requires a functional sulfur-amino acid regulatory network. J Biol Chem 275:32611–32616

    Article  PubMed  CAS  Google Scholar 

  7. Brama M, Politi L, Santini P et al (2012) Cadmium-induced apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated protein kinases pathways. J Endocrinol Invest 35:198–208

    PubMed  CAS  Google Scholar 

  8. Pathak N, Mitra S, Khandelwal S (2013) Cadmium induces thymocyte apoptosis via caspase-dependent and caspase-independent pathways. J Biochem Mol Toxicol 27:193–203

    Article  PubMed  CAS  Google Scholar 

  9. Chang KC, Hsu CC, Liu SH et al (2013) Cadmium induces apoptosis in pancreatic β-cells through a mitochondria-dependent pathway: the role of oxidative stress-mediated c-jun N-terminal kinase activation. PLoS One, 8(2) doi:10.1371/journal.pone.0054374

  10. Sinha K, Pal PB, Sil PC (2014) Cadmium (Cd(2 +)) exposure differentially elicits both cell proliferation and cell death related responses in SK-RC-45. Toxicol In Vitro 28:307–318

    Article  PubMed  CAS  Google Scholar 

  11. Chen S, Ren Q, Zhang J, et al. (2013) N-acetyl-l-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain. Neuropathol Appl Neurobiol. doi:10.1111/nan.12103

  12. Waalkes MP (2003) Cadmium carcinogenesis. Mutat Res 533:107–120

    Article  PubMed  CAS  Google Scholar 

  13. Brama M, Gnessi L, Basciani S et al (2007) Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol 264:102–108

    Article  PubMed  CAS  Google Scholar 

  14. Ponce E, Aquino NB, Louie MC (2013) Chronic cadmium exposure stimulates SDF-1 expression in an ERα dependent manner. PLoS One 8(8):e72639. doi:10.1371/journal.pone.0072639

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Yano CL, Marcondes MC (2005) Cadmium chloride-induced oxidative stress in skeletal muscle cells in vitro. Free Radic Biol Med 39:1378–1384

    Article  PubMed  CAS  Google Scholar 

  16. Derbré F, Gratas-Delamarche A, Gómez-Cabrera MC et al (2014) Inactivity-induced oxidative stress: a central role in age-related sarcopenia? Eur J Sport Sci 14(Suppl 1):S98–S108

    Article  PubMed  Google Scholar 

  17. Siparsky PN, Kirkendall DT, Garrett WE Jr (2014) Muscle changes in aging: understanding sarcopenia. Sports Health 6:36–40

    Article  PubMed  Google Scholar 

  18. Rom O, Kaisari S, Aizenbud D et al (2012) Identification of possible cigarette smoke constituents responsible for muscle catabolism. J Muscle Res Cell Motil 33:199–208

    Article  PubMed  CAS  Google Scholar 

  19. Rom O, Kaisari S, Aizenbud D et al (2012) Lifestyle and sarcopenia-etiology, prevention, and treatment. Rambam Maimonides Med J 3(4):e0024. doi:10.5041/RMMJ.10091

    Article  PubMed  PubMed Central  Google Scholar 

  20. Castillo EM, Goodman-Gruen D, Kritz-Silverstein D et al (2003) Sarcopenia in elderly men and women: the Rancho Bernardo study. Am J Prev Med 25:226–231

    Article  PubMed  Google Scholar 

  21. Lee JS, Auyeung TW, Kwok T et al (2007) Associated factors and health impact of sarcopenia in older Chinese men and women: a cross-sectional study. Gerontology 53:404–410

    Article  PubMed  Google Scholar 

  22. Szulc P, Duboeuf F, Marchand F et al (2004) Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study. Am J Clin Nutr 80:496–503

    PubMed  CAS  Google Scholar 

  23. Montes de Oca M, Loeb E, Torres SH et al (2008) Peripheral muscle alterations in non-COPD smokers. Chest 133:13–18. doi:10.1378/chest.07-1592

    Article  PubMed  CAS  Google Scholar 

  24. Petersen AM, Magkos F, Atherton P et al (2007) Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. Am J Physiol Endocrinol Metab 293:E843–E848

    Article  PubMed  CAS  Google Scholar 

  25. Wannenes F, Caprio M, Gatta L et al (2008) Androgen receptor expression during C2C12 skeletal muscle cell line differentiation. Mol Cell Endocrinol 292:11–19

    Article  PubMed  CAS  Google Scholar 

  26. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−∆∆Ct method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  27. Rom O, Kaisari S, Aizenbud D et al (2013) Cigarette smoke and muscle catabolism in C2 myotubes. Mech Ageing Dev 134:24–34

    Article  PubMed  CAS  Google Scholar 

  28. Guo K, Walsh K (1997) Inhibition of myogenesis by multiple cyclin-Cdk complexes. Coordinate regulation of myogenesis and cell cycle activity at the level of E2F. J Biol Chem 272:791–797

    Article  PubMed  CAS  Google Scholar 

  29. Halevy O, Piestun Y, Allouh MZ et al (2004) Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal. Dev Dyn 231:489–502

    Article  PubMed  CAS  Google Scholar 

  30. Tidball JG (1995) Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 27:1022–1032

    Article  PubMed  CAS  Google Scholar 

  31. Huard J, Li Y, Fu FH (2002) Muscle injuries and repair: current trends in research. J Bone Jt Surg Am 84-A: 822–32

  32. Jarvinen TA, Järvinen TL, Kääriäinen M et al (2005) Muscle injuries: biology and treatment. Am J Sports Med 33:745–764

    Article  PubMed  Google Scholar 

  33. Collins CA, Olsen I, Zammit PS et al (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122:289–301

    Article  PubMed  CAS  Google Scholar 

  34. Sherwood RI, Christensen JL, Conboy IM et al (2004) Isolation of adult mouse myogenic progenitors: functional heterogeneity of cells within and engrafting skeletal muscle. Cell 119:543–554

    Article  PubMed  CAS  Google Scholar 

  35. Zammit PS, Heslop L, Hudon V et al (2002) Kinetics of myoblast proliferation show that resident satellite cells are competent to fully regenerate skeletal muscle fibers. Exp Cell Res 281:39–49

    Article  PubMed  CAS  Google Scholar 

  36. Zammit PS, Partridge TA, Yablonka-Reuveni Z (2006) The skeletal muscle satellite cell: the stem cell that came in from the cold. J Histochem Cytochem 54:1177–1191

    Article  PubMed  CAS  Google Scholar 

  37. Collins CA, Gnocchi VF, White RB et al (2009) Integrated functions of Pax3 and Pax7 in the regulation of proliferation, cell size and myogenic differentiation. PLoS One 4(2):e4475. doi:10.1371/journal.pone.0004475

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zammit PS, Golding JP, Nagata Y et al (2004) Muscle satellite cells adopt divergent fates: a mechanism for self-renewal? J Cell Biol 166:347–357

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Conboy IM, Rando TA (2002) The regulation of notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev Cell 3:397–409

    Article  PubMed  CAS  Google Scholar 

  40. Day K, Shefer G, Richardson JB et al (2007) Nestin-GFP reporter expression defines the quiescent state of skeletal muscle satellite cells. Dev Biol 304:246–259

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Shinin V, Gayraud-Morel B, Gomès D et al (2006) Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nat Cell Biol 8:677–687

    Article  PubMed  CAS  Google Scholar 

  42. Olguin HC, Olwin BB (2004) Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal. Dev Biol 275:375–388

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Velders M, Diel P (2013) How sex hormones promote skeletal muscle regeneration. Sports Med 43:1089–1100

    Article  PubMed  Google Scholar 

  44. Greising SM, Baltgalvis KA, Kosir AM, Moran AL, Warren GL, Lowe DA (2011) Estradiol’s beneficial effect on murine muscle function is independent of muscle activity. J Appl Physiol 110:109–115

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Ronkainen PH, Kovanen V, Alén M, Pöllänen E, Palonen EM, Ankarberg-Lindgren C, Hämäläinen E, Turpeinen U, Kujala UM, Puolakka J, Kaprio J, Sipilä S (2009) Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs. J Appl Physiol 107:25–33

    Article  PubMed  CAS  Google Scholar 

  46. Rom O, Kaisari S, Aizenbud D et al (2012) Sarcopenia and smoking: a possible cellular model of cigarette smoke effects on muscle protein breakdown. Ann NY Acad Sci 1259:47–53

    Article  PubMed  CAS  Google Scholar 

  47. Rani A, Kumar A, Lal A et al (2014) Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res 24:378–399

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

FW is supported by an ELI-Lilly grant. LiSa laboratories are a Jont-Venture between Eli Lilly Firenze and Sapienza University of Rome, Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, Sapienza University of Rome. SM is grateful to prof. Fabio Pigozzi for his support. FW is kindly supported by an ELI Lilly fellowship. Research was funded by PRIN 2011 052013 to SM, Project PON01_00829 (by MIUR, Ministry of Economic Development and European Community) to AL, PRIN 07 2013 to FB.

Conflict of interest

The authors declared no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. Migliaccio.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Papa, V., Wannenes, F., Crescioli, C. et al. The environmental pollutant cadmium induces homeostasis alteration in muscle cells in vitro. J Endocrinol Invest 37, 1073–1080 (2014). https://doi.org/10.1007/s40618-014-0145-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-014-0145-y

Keywords

Navigation