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.
Similar content being viewed by others
Abbreviations
- Cd:
-
Cadmium
- CdCl2 :
-
Cadmium chloride
- MyHC:
-
Myosin heavy chain
References
Järup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238:201–208
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
Bernhoft RA (2013) Cadmium toxicity and treatment. Sci World J
Beyersmann D, Hechtenberg S (1997) Cadmium, gene regulation, and cellular signaling in mammalian cells. Toxicol Appl Pharmacol 144:247–261
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
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
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
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
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
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
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
Waalkes MP (2003) Cadmium carcinogenesis. Mutat Res 533:107–120
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
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
Yano CL, Marcondes MC (2005) Cadmium chloride-induced oxidative stress in skeletal muscle cells in vitro. Free Radic Biol Med 39:1378–1384
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
Siparsky PN, Kirkendall DT, Garrett WE Jr (2014) Muscle changes in aging: understanding sarcopenia. Sports Health 6:36–40
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
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
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
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
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
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
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
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
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
Rom O, Kaisari S, Aizenbud D et al (2013) Cigarette smoke and muscle catabolism in C2 myotubes. Mech Ageing Dev 134:24–34
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
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
Tidball JG (1995) Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 27:1022–1032
Huard J, Li Y, Fu FH (2002) Muscle injuries and repair: current trends in research. J Bone Jt Surg Am 84-A: 822–32
Jarvinen TA, Järvinen TL, Kääriäinen M et al (2005) Muscle injuries: biology and treatment. Am J Sports Med 33:745–764
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
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
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
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
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
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
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
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
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
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
Velders M, Diel P (2013) How sex hormones promote skeletal muscle regeneration. Sports Med 43:1089–1100
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
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
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
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
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
Corresponding author
Rights and permissions
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40618-014-0145-y