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Cell Biochemistry and Biophysics

, Volume 71, Issue 2, pp 649–656 | Cite as

STAT5 Reactivation by Catechin Modulates H2O2-Induced Apoptosis Through miR-182/FOXO1 Pathway in SK-N-MC Cells

  • Ali Gheysarzadeh
  • Razieh YazdanparastEmail author
Original Paper

Abstract

It has been suggested that oxidative stress-induced apoptosis is a major contributing factor in the pathogenesis of Alzheimer’s and Parkinson’s diseases. However, the molecular mechanism of the oxidative stress-associated apoptosis is far to be elucidated. Herein, we investigated whether STAT5, which is involved in many signaling pathways, is affected by oxidative stress. Previously, it has been shown that STAT5 is a direct activator of miR-182 which is in turn a robust inhibitor of FOXO1. Our results showed that oxidative stress inactivated STAT5 may be in a JAK2-independent manner. Thus, under oxidative stress and miR-182 down-regulation, FOXO1 has the opportunity to be translated leading to FOXO1 over-expression. Finally, pro-apoptotic gene targets of FOXO1 e.g., Bim and Bax are up-regulated leading to apoptosis. To further confirm such events, we also demonstrated that Catechin, a well-known natural antioxidant, partially restored both the STAT5 activation and miR-182 expression resulting in cell survival. To the best of our knowledge, this is the first study demonstrating that STAT5/miRNA-182 negatively regulates FOXO1 in response to oxidative stress.

Keywords

Catechin miR-182 Oxidative stress SK-N-MC cells STAT5 

Abbreviations

ROS

Reactive oxygen species

FOXO1

Forkhead box protein O1

STAT

Signal transducers and activators of transcription

JAK

Janus tyrosine kinase

Notes

Acknowledgments

The authors appreciate the financial support of this investigation by the Research Council of University of Tehran.

References

  1. 1.
    Sies, H. (2000). Oxidative stress: From basic research to clinical application. The American Journal of Medicine, 91, S31–S38.CrossRefGoogle Scholar
  2. 2.
    Mittler, R. (2002). Oxidative stress, antioxidants and stress tolerance. Trends in Plant Science, 7, 405–410.PubMedCrossRefGoogle Scholar
  3. 3.
    Baynes, J. W. (1991). Role of oxidative stress in development of complications in diabetes. Diabetes, 40, 405–412.PubMedCrossRefGoogle Scholar
  4. 4.
    Coyle, J. T., & Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders. Science, 262, 689–695.PubMedCrossRefGoogle Scholar
  5. 5.
    Halliwell, B. (2007). Oxidative stress and cancer: have we moved forward? Biochemical Journal, 401, 1–11.PubMedCrossRefGoogle Scholar
  6. 6.
    Thannickal, V. J., & Fanburg, B. L. (2000). Reactive oxygen species in cell signaling. American Journal of Physiology-Lung Cellular and Molecular Physiology., 279, L1005–L1028.PubMedGoogle Scholar
  7. 7.
    Patel, R. P., Moellering, D., Murphy-Ullrich, J., Jo, H., Beckman, J. S., & Darley-Usmar, V. M. (2000). Cell signaling by reactive nitrogen and oxygen species in atherosclerosis. Free Radical Biology and Medicine, 28, 1780–1794.PubMedCrossRefGoogle Scholar
  8. 8.
    Hensley, K., Robinson, K. A., Gabbita, S. P., Salsman, S., & Floyd, R. A. (2000). Reactive oxygen species, cell signaling, and cell injury. Free Radical Biology and Medicine, 28, 1456–1462.PubMedCrossRefGoogle Scholar
  9. 9.
    Ruch, R. J., Cheng, S., & Klaunig, J. E. (1989). Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis, 10, 1003–1008.PubMedCrossRefGoogle Scholar
  10. 10.
    Leung, L. K., Su, Y., Chen, R., Zhang, Z., Huang, Y., & Chen, Z. Y. (2001). Theaflavins in black tea and catechins in green tea are equally effective antioxidants. The Journal of nutrition., 131, 2248–2251.PubMedGoogle Scholar
  11. 11.
    Mandel, S., Amit, T., Reznichenko, L., Weinreb, O., & Youdim, M. B. H. (2006). Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Molecular Nutrition & Food Research, 50, 229–234.CrossRefGoogle Scholar
  12. 12.
    Rawlings, J. S., Rosler, K. M., & Harrison, D. A. (2004). The JAK/STAT signaling pathway. Journal of Cell Science, 117, 1281–1283.PubMedCrossRefGoogle Scholar
  13. 13.
    Gamero, A. M., & Larner, A. C. (2001). Vanadate facilitates interferon α-mediated apoptosis that is dependent on the Jak/Stat pathway. Journal of Biological Chemistry, 276, 13547–13553.PubMedGoogle Scholar
  14. 14.
    Weber-Nordt, R., Mertelsmann, R., & Finke, J. (1998). The JAK-STAT pathway: signal transduction involved in proliferation, differentiation and transformation. Leukemia & lymphoma., 28, 459–467.Google Scholar
  15. 15.
    Lu, Y., Zhou, J., Xu, C., Lin, H., Xiao, J., Wang, Z., et al. (2008). JAK/STAT and PI3 K/AKT pathways form a mutual transactivation loop and afford resistance to oxidative stress-induced apoptosis in cardiomyocytes. Cellular Physiology and Biochemistry, 21, 305–314.PubMedCrossRefGoogle Scholar
  16. 16.
    Simon, A. R., Rai, U., Fanburg, B. L., & Cochran, B. H. (1998). Activation of the JAK-STAT pathway by reactive oxygen species. American Journal of Physiology-Cell Physiology., 275, C1640–C1652.Google Scholar
  17. 17.
    Mazière, C., Conte, M. A., & Mazière, J. C. (2001). Activation of JAK2 by the oxidative stress generated with oxidized low-density lipoprotein. Free Radical Biology and Medicine, 31, 1334–1340.PubMedCrossRefGoogle Scholar
  18. 18.
    Sandberg, E. M., & Sayeski, P. P. (2004). Jak2 tyrosine kinase mediates oxidative stress-induced apoptosis in vascular smooth muscle cells. Journal of Biological Chemistry, 279, 34547–34552.PubMedCrossRefGoogle Scholar
  19. 19.
    Madamanchi, N. R., Li, S., Patterson, C., & Runge, M. S. (2001). Reactive oxygen species regulate heat-shock protein 70 via the JAK/STAT pathway. Arteriosclerosis, Thrombosis, and Vascular Biology, 21, 321–326.PubMedCrossRefGoogle Scholar
  20. 20.
    Yu, H., Zhi, J., Cui, Y., Tang, E., Sun, S., Feng, J., et al. (2006). Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells. Apoptosis, 11, 931–941.PubMedCrossRefGoogle Scholar
  21. 21.
    Buitenhuis, M., Coffer, P. J., & Koenderman, L. (2004). Signal transducer and activator of transcription 5 (STAT5). The international journal of biochemistry & cell biology., 36, 2120–2124.CrossRefGoogle Scholar
  22. 22.
    Ambrosio, R., Fimiani, G., Monfregola, J., Sanzari, E., De Felice, N., Salerno, M. C., et al. (2002). The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter. Gene, 285, 311–318.PubMedCrossRefGoogle Scholar
  23. 23.
    Socolovsky, M., Fallon, A. E. J., Wang, S., Brugnara, C., & Lodish, H. F. (1999). Fetal anemia and apoptosis of red cell progenitors in Stat5a/5b mice: A direct role for Stat5 in Bcl-XL induction. Cell, 98, 181–191.PubMedCrossRefGoogle Scholar
  24. 24.
    Lord, J. D., McIntosh, B. C., Greenberg, P. D., & Nelson, B. H. (2000). The IL-2 receptor promotes lymphocyte proliferation and induction of the c-myc, bcl-2, and bcl-x genes through the trans-activation domain of Stat5. The Journal of Immunology, 164, 2533–2541.PubMedCrossRefGoogle Scholar
  25. 25.
    Dudley, A. C., Thomas, D., Best, J., & Jenkins, A. (2004). The STATs in cell stress-type responses. Cell Communication and Signaling, 2, 8–13.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Debierre-Grockiego, F. (2004). Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies. Apoptosis, 9, 717–728.PubMedCrossRefGoogle Scholar
  27. 27.
    Inui, M., Martello, G., & Piccolo, S. (2010). MicroRNA control of signal transduction. Nature Reviews Molecular Cell Biology, 11, 252–263.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim, V. N., Han, J., & Siomi, M. C. (2009). Biogenesis of small RNAs in animals. Nature Reviews Molecular Cell Biology, 10, 126–139.PubMedCrossRefGoogle Scholar
  29. 29.
    Stark, A., Brennecke, J., Bushati, N., Russell, R. B., & Cohen, S. M. (2005). Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3′ UTR evolution. Cell, 123, 1133–1146.PubMedCrossRefGoogle Scholar
  30. 30.
    Griffiths-Jones, S. (2010). miRBase: microRNA sequences and annotation. Current Protocols in Bioinformatics., 12, 1–12.Google Scholar
  31. 31.
    Miska, E. A. (2005). How microRNAs control cell division, differentiation and death. Current Opinion in Genetics & Development, 15, 563–568.CrossRefGoogle Scholar
  32. 32.
    Li, G., Miskimen, K. L., Wang, Z., Xie, X. Y., Brenzovich, J., Ryan, J. J., et al. (2010). STAT5 requires the N-domain for suppression of miR15/16, induction of bcl-2, and survival signaling in myeloproliferative disease. Blood, 115, 1416–1424.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    O’Neill, L. A. J. (2010). Outfoxing Foxo1 with miR-182. Nature Immunology, 11, 983–984.PubMedCrossRefGoogle Scholar
  34. 34.
    Stittrich, A. B., Haftmann, C., Sgouroudis, E., Kühl, A. A., Hegazy, A. N., Panse, I., et al. (2010). The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nature Immunology, 11, 1057–1062.PubMedCrossRefGoogle Scholar
  35. 35.
    Guttilla, I. K., & White, B. A. (2009). Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. Journal of Biological Chemistry, 284, 23204–23216.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Furukawa-Hibi, Y., Kobayashi, Y., Chen, C., & Motoyama, N. (2005). FOXO transcription factors in cell-cycle regulation and the response to oxidative stress. Antioxidants & Redox Signaling, 7, 752–760.CrossRefGoogle Scholar
  37. 37.
    Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., et al. (2007). FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell, 128, 325–339.PubMedCrossRefGoogle Scholar
  38. 38.
    Gheysarzadeh, A., & Yazdanparast, R. (2012). Inhibition Of H 2O 2 Induced Cell Death Through Foxo1 Modulation By Euk-172 In Sk-N-Mc Cells. European Journal of Pharmacology, 697, 47–52.PubMedCrossRefGoogle Scholar
  39. 39.
    D’Autréaux, B., & Toledano, M. B. (2007). ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nature Reviews Molecular Cell Biology, 8, 813–824.PubMedCrossRefGoogle Scholar
  40. 40.
    Choi, W. S., Eom, D. S., Han, B. S., Kim, W. K., Han, B. H., Choi, E. J., et al. (2004). Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8-and-9-mediated apoptotic pathways in dopaminergic neurons. Journal of Biological Chemistry, 279, 20451–20460.PubMedCrossRefGoogle Scholar
  41. 41.
    Raza, H., & John, A. (2007). In vitro protection of reactive oxygen species-induced degradation of lipids, proteins and 2-deoxyribose by tea catechins. Food and Chemical Toxicology, 45, 1814–1820.PubMedCrossRefGoogle Scholar
  42. 42.
    Ihle, J. N. (2001). The Stat family in cytokine signaling. Current Opinion in Cell Biology, 13, 211–217.PubMedCrossRefGoogle Scholar
  43. 43.
    Nosaka, T., Kawashima, T., Misawa, K., Ikuta, K., Mui, A. L. F., & Kitamura, T. (1999). STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. The EMBO Journal., 18, 4754–4765.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Byts, N., Samoylenko, A., Fasshauer, T., Ivanisevic, M., Hennighausen, L., Ehrenreich, H., et al. (2008). Essential role for Stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin. Cell Death and Differentiation, 15, 783–792.PubMedCrossRefGoogle Scholar
  45. 45.
    Cholez, E., Debuysscher, V., Bourgeais, J., Boudot, C., Leprince, J., Tron, F., et al. (2012). Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells. Leukemia, 26(11), 2390–2397.PubMedCrossRefGoogle Scholar
  46. 46.
    Shimoda, K., Feng, J., Murakami, H., Nagata, S., Watling, D., Rogers, N. C., et al. (1997). Jak1 plays an essential role for receptor phosphorylation and Stat activation in response to granulocyte colony-stimulating factor. Blood, 90, 597–604.PubMedGoogle Scholar
  47. 47.
    Caffarel, M. M., Zaragoza, R., Pensa, S., Li, J., Green, A. R., & Watson, C. J. (2011). Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling, promotes alveologenesis and resistance to cell death, and contributes to tumourigenesis. Cell Death and Differentiation, 19, 511–522.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Kirken, R. A., Rui, H., Malabarba, M. G., Howard, O., Kawamura, M., O’Shea, J. J., et al. (1995). Activation of JAK3, but not JAK1, is critical for IL-2-induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain. Cytokine, 7, 689–700.PubMedCrossRefGoogle Scholar
  49. 49.
    Moskwa, P., Buffa, F. M., Pan, Y., Panchakshari, R., Gottipati, P., Muschel, R. J., et al. (2011). miR-182-mediated down-regulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Molecular Cell, 41, 210–220.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Zhang, L., Liu, T., Huang, Y., & Liu, J. (2011). microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. International Journal of Molecular Medicine, 28, 381–388.PubMedGoogle Scholar
  51. 51.
    Segura, M. F., Hanniford, D., Menendez, S., Reavie, L., Zou, X., Alvarez-Diaz, S., et al. (2009). Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proceedings of the National Academy of Sciences, 106, 1814–1819.CrossRefGoogle Scholar
  52. 52.
    Lam, E., Francis, R., & Petkovic, M. (2006). FOXO transcription factors: key regulators of cell fate. Biochemical Society Transactions, 34, 722–726.PubMedCrossRefGoogle Scholar
  53. 53.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 193, 265–275.PubMedGoogle Scholar
  54. 54.
    Abmayr, S. M., Carrozza, M. J., & Workman, J. L. (2003). Preparation of nuclear and cytoplasmic extracts from mammalian cells. Current protocols in pharmacology. John Wiley, 12(1), 1.Google Scholar
  55. 55.
    Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-[Delta][Delta] CT method. Methods, 25, 402–408.PubMedCrossRefGoogle Scholar
  56. 56.
    Chen, C., Ridzon, D. A., Broomer, A. J., Zhou, Z., Lee, D. H., Nguyen, J. T., et al. (2005). Real-time quantification of microRNAs by stem–loop RT–PCR. Nucleic Acids Research, 33, e179–e179.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Biochemistry and BiophysicsUniversity of TehranTehranIran

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