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Abstract:

Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5 mM; no toxic doses in these cells. A dose of 5 mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72±10 [DCN-5] vs 169±15 [DC], p<0.01), as well in Oil Red O stained neutral lipid content (120±2 [DCN-5] vs 139±12 [DC], p<0.01). Molecular mechanisms responsible for adipogenic differentiation involve increase of the expression of phosphoERK1/2 and phosphoJNK, 5 mM NAC treatment inhibited both pERK1/2 and pJNK protein levels. We also evaluated the mitotic clonal expansion (MCE) which takes place during adipogenesis and observed an increase in DC at a rate of 1.5 cells number compared to CC at day 2, whereas the highest doses of NAC significantly inhibited MCE. Our results suggest that NAC inhibits lipid accumulation and the MAPK phosphorylation in mouse embryonic fibroblasts during adipogenic differentiation and further contribute to probe the importance of cellular redox environment in adipogenesis. © 2016 The Authors.

Registro:

Documento: Artículo
Título:N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes
Autor:Pieralisi, A.; Martini, C.; Soto, D.; Vila, M.C.; Calvo, J.C.; Guerra, L.N.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires - IQUIBICEN, CONICET, Intendente Güiraldes 2160, Pabellón 2, Buenos Aires, 1428, Argentina
IBYME, CONICET, Vuelta de Obligado 2490, Buenos Aires, 1428, Argentina
Palabras clave:Adipogenesis; Antioxidants; Kinases; Lipids; MEF; N-acetylcysteine; acetylcysteine; Janus kinase; mitogen activated protein kinase; phosphoERK; phosphoJNK; phosphoprotein; triacylglycerol; unclassified drug; acetylcysteine; phosphotransferase; adipocyte; adipogenesis; animal cell; animal tissue; antioxidant activity; Article; cell count; cell differentiation; cell function; cell level; cell proliferation; cell stress; cell viability; concentration response; controlled study; disease model; drug cytotoxicity; drug effect; embryo; enzyme phosphorylation; lipid storage; mitotic clonal expansion; mouse; nonhuman; obesity; priority journal; procedures concerning cells; protein expression; protein lipid interaction; signal transduction; 3T3-L1 cell line; adipocyte; animal; cytology; drug effects; fibroblast; lipid metabolism; mammalian embryo; metabolism; phosphorylation; 3T3-L1 Cells; Acetylcysteine; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Embryo, Mammalian; Fibroblasts; Lipid Metabolism; Mice; Phosphorylation; Phosphotransferases
Año:2016
Volumen:9
Página de inicio:39
Página de fin:44
DOI: http://dx.doi.org/10.1016/j.redox.2016.05.006
Título revista:Redox Biology
Título revista abreviado:Redox Biol.
ISSN:22132317
CAS:acetylcysteine, 616-91-1; Janus kinase, 161384-16-3; mitogen activated protein kinase, 142243-02-5; phosphotransferase, 9031-09-8, 9031-44-1; Acetylcysteine; Phosphotransferases
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_22132317_v9_n_p39_Pieralisi

Referencias:

  • Liu, G.S., Chan, E.C., Higuchi, M., Dusting, G.J., Jiang, F., Redox mechanisms in regulation of adipocyte differentiation: beyond a general stress response (2012) Cells, 1, pp. 976-993
  • Calzadilla, P., Gomez-Serrano, M., García-Santos, E., Schiappacasse, A., Abalde, Y., Calvo, J.C., Peral, B., Guerra, L.N., N- Acetylcysteine affects obesity proteins expression in 3T3-L1 (2013) Redox Rep., 18, pp. 210-218
  • Calzadilla, P., Sapochnik, D., Cosentino, S., Diz, V., Dicelio, L., Calvo, J.C., Guerra, L.N., N-acetylcysteine reduces markers of differentiation in 3T3-L1 adipocytes (2011) Int. J. Mol. Sci., 12, pp. 6936-6951
  • Prusty, D., Park, B.H., Davis, K.E., Farmer, S.R., Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma) and C/EBP alpha gene expression during differentiation of 3T3-L1 preadipocytes (2002) J. Biol. Chem., 27, pp. 46226-46232
  • Donzelli, E., Lucchini, C., Ballarini, E., Scuteri, A., Carini, F., Tredici, G., Miloso, M., ERK1 and ERK 2 are involved in recruitment and maturation of human mesenchymal stem cells induced to adipogenic differentiation (2011) J. Mol. Cell Biol., 3, pp. 123-131
  • Bost, F., Aouadi, M., Caron, L., Binetruy, B., The role of MAPKs in adipocyte differentiation and obesity (2005) Biochimie, 87, pp. 51-56
  • Gehart, H., Kumpf, S., Ittner, A., Ricci, R., MAPK signaling in cellular metabolism: stress or wellness? (2010) EMBO Rep., 11, pp. 834-840
  • Kim, J.R., Ryu, H., Chung, H.J., Lee, J.H., Kim, S.W., Kwun, W.H., Baek, S.H., Kim, J.H., Association of anti-obesity activity of N-acteylcysteine with metalothionein-II down-regulation. Experimental (2006) Mol. Med, 30, pp. 162-172
  • Araki, S., Dobashi, K., Kugo, K., Yamamoto, Y., Asayama, K., Shirahata, A., N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plaminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes (2006) Life Sci., 79, pp. 2405-2412
  • Lukas, J., Bartkova, J., Rohde, M., Strauss, M., Bartek, J., Cyclin D1 is dispensable for G1 control in retinoblastoma gene-deficient cells independently of cdk4 activity (1995) Mol. Cell Biol., 15, pp. 2600-2611
  • Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal. Biochem, 72, pp. 248-254
  • Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays (1983) J. Immunol. Methods, 65, pp. 55-63
  • (2003) Statistix 8, , Mcgraw-Hill/Irwin, Tallahassee, FL, USA
  • Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Brirringer, M., Kiehntopt, M., Stumvoll, M., Bluher, M., Antioxidants prevents health promoting effects of physical exercise in humans (2009) Proc. Nat. Acad. Sciences USA, 106, pp. 8665-8670
  • Uto-Kondo, H., Ohmori, R., Kiyose, C., Kishimoto, Y., Saito, H., Igarashi, O., Kondo, K., Tocotrienol suppresses adipocyte differentiation and AKT phosphorylation in 3T3-L1 preadipocytes (2009) J. Nutr., 139, pp. 51-57
  • Wang, T., Si, Y., Shirihai, O.S., Si, H., Schultz, V., Corkey, R.F., Respiration in adipocytes is inhibited by reactive oxygen species (2010) Obesity, 18, pp. 1493-1502
  • Guo, W., Li, Y., Liang, W., Wong, S., Apovian, C., Kirkland, B., Beta-mercaptoethanol suppresses inflammation and induces adipogenic differentiation in 3T3-F442 murine preadipocytes (2012) PLoS One, 7. , e40958
  • Kim, E.K., Choi, E.J., Compromised MAPK signaling in human diseases: an update (2015) Arch. Toxicol., 89, pp. 867-882
  • Poudel, B., Lim, S., Ki, H., Nepali, S., Lee, Y., Kim, D., Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 and modulates fat accumulation in obese mice (2014) Int. J. Mol. Med., 34, pp. 1401-1408
  • Li, K.K., Liu, C.L., Shiu, H.T., Wong, H.L., Siu, W.S., Zhan, C., Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes (2016) Sci. Rep., 6, pp. 20172-20183

Citas:

---------- APA ----------
Pieralisi, A., Martini, C., Soto, D., Vila, M.C., Calvo, J.C. & Guerra, L.N. (2016) . N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes. Redox Biology, 9, 39-44.
http://dx.doi.org/10.1016/j.redox.2016.05.006
---------- CHICAGO ----------
Pieralisi, A., Martini, C., Soto, D., Vila, M.C., Calvo, J.C., Guerra, L.N. "N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes" . Redox Biology 9 (2016) : 39-44.
http://dx.doi.org/10.1016/j.redox.2016.05.006
---------- MLA ----------
Pieralisi, A., Martini, C., Soto, D., Vila, M.C., Calvo, J.C., Guerra, L.N. "N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes" . Redox Biology, vol. 9, 2016, pp. 39-44.
http://dx.doi.org/10.1016/j.redox.2016.05.006
---------- VANCOUVER ----------
Pieralisi, A., Martini, C., Soto, D., Vila, M.C., Calvo, J.C., Guerra, L.N. N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes. Redox Biol. 2016;9:39-44.
http://dx.doi.org/10.1016/j.redox.2016.05.006