DOI QR코드

DOI QR Code

Regulation of melanocyte apoptosis by Stathmin 1 expression

  • Zhang, Yan (Department of Biochemistry and Molecular Biology, Zhongshan Medical College, Sun Yat-sen University) ;
  • Xiong, Jianjun (Department of Biochemistry and Molecular Biology, Zhongshan Medical College, Sun Yat-sen University) ;
  • Wang, Jiali (Department of Biochemistry and Molecular Biology, Zhongshan Medical College, Sun Yat-sen University) ;
  • Shi, Xianping (Department of Biochemistry and Molecular Biology, Zhongshan Medical College, Sun Yat-sen University) ;
  • Bao, Guodong (DaAn Gene Co., Ltd., Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China) ;
  • Zhang, Yang (DaAn Gene Co., Ltd., Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China) ;
  • Zhu, Zhenyu (Department of Biochemistry and Molecular Biology, Zhongshan Medical College, Sun Yat-sen University)
  • Published : 2008.11.30

Abstract

Undesirable hyperpigmentation that can arise from increased melanocyte activity may be alleviated by targeting active melanocytes for apoptosis. The role of Stathmin 1 as an important regulator of microtubule dynamics is well documented. The current study examined the potential of Stathmin 1-targeting strategies in eliminating active melanocytes. A vector to overexpress Stathmin 1 and vectors to express three distinct small hairpin RNAs to knockdown Stathmin 1 expression in normal melanocytes were produced and in cell cultures acted accordingly. Both overexpression and knockdown of Stathmin 1 led to a marked increase in melanocyte apoptosis, as indicated by the accumulation of apoptotic cells and increased levels of cleaved caspase-3. Both up- and down-regulation of Stathmin 1 expression inhibited the activity of differentiated melanocytes, as indicated by decreases in both melanin production and tyrosinase activity. Taken together, these results indicate that hyperactive melanocytes can be inhibited by altering Stathmin 1 expression.

Keywords

References

  1. Westerhof, W. (2006) The discovery of the human melanocyte. Pigment Cell Res. 19, 183-193 https://doi.org/10.1111/j.1600-0749.2006.00313.x
  2. Grant, W.B., Strange, R.C. and Garland, C.F. (2003) Sunshine is good medicine. The health benefits of ultraviolet-B induced vitamin D production. J. Cosmet. Dermatol. 2, 86-98 https://doi.org/10.1111/j.1473-2130.2004.00041.x
  3. Liu A, Stadelmann C, Moscarello M, Bruck W, Sobel A, Mastronardi FG, Casaccia-Bonnefil P. (2005) Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders. J. Neurosci. 3, 737-747
  4. Rubin, C.I. and Atweh, G.F. (2004) The Role of Stathmin in the Regulation of the Cell Cycle. Atweh Journal of Cellular Biochemistry. 93, 242-250 https://doi.org/10.1002/jcb.20187
  5. Mistry, S.J. and Atweh, G.F. (2002). Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. Mt Sinai J. Med. 5, 299-304
  6. Toda T, Sugimoto M, Omori A, Matsuzaki T, Furuichi Y, Kimura N. (2000) Proteomic analysis of Epstein-Barr virus transformed human B-lymphoblastoid cell lines before and after immortalization. Electrophoresis. 21, 1814-1822 https://doi.org/10.1002/(SICI)1522-2683(20000501)21:9<1814::AID-ELPS1814>3.0.CO;2-#
  7. Hayashi K, Pan Y, Shu H, Ohshima T, Kansy JW, White CL 3rd, Tamminga CA, Sobel A, Curmi PA, Mikoshiba K, Bibb JA. (2006) Phosphorylation of the tubulin-binding protein, stathmin, by Cdk5 and MAP kinases in the brain. J. Neurochem. 1, 237-250
  8. Mizumura K, Takeda K, Hashimoto S, Horie T, Ichijo H. (2006) Identification of Op18/stathmin as a potential target of ASK1-p38 MAP kinase cascade. J. Cell Physiol. 2, 363-370
  9. Marklund U, Larsson N, Gradin HM, Brattsand G, Gullberg M. (1996) Oncoprotein 18 is a phosphorylationresponsive regulator of microtubule dynamics. The EMBO Journal. 19, 5290-5298
  10. Gradin HM, Larsson N, Marklund U, Gullberg M. (1998) Regulation of microtubule dynamics by extracellular signals: cAMP-dependent protein kinase switches off the activity of oncoprotein 18 in intact cells. J. Cell Biol. 1, 131-141
  11. Belmont, L.D. and Mitchison, T.J. (1996). Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell. 4, 623-631
  12. Jourdain, L., Curmi, P. and Sobel, A. (1997). Stathmin: a tubulin-sequestering protein which forms a ternary T2S complex with two tubulin molecules. Biochemistry 36, 10817-10821 https://doi.org/10.1021/bi971491b
  13. Caldwell BD, Darlington DN, Penzes P, Johnson RC, Eipper BA, Mains RE. (1999) The novel kinase peptidylglycine alpha- amidating monooxygenase cytosolic interactor protein 2 interacts with the cytosolic routing determinants of the peptide processing enzyme peptidylglycine alpha- amidating monooxygenase. J. Biol. Chem. 49, 34646-34656
  14. Bieche I, Manceau V, Curmi PA, Laurendeau I, Lachkar S, Leroy K, Vidaud D, Sobel A, Maucuer A. (2003) Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human. Molecular Brain Research. 114, 55-64 https://doi.org/10.1016/S0169-328X(03)00132-3
  15. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498 https://doi.org/10.1038/35078107
  16. Kim, J., Kim, H., Lee, Y., Yang, K., Byun, S. and Han, K. (2006) A Simple and Economical Short-oligonucleotide-based Approach to shRNA Generation. JBMB. 39, 329-334
  17. Sui G, Soohoo C, Affar el B, Gay F, Shi Y, Forrester WC, Shi Y. (2002) A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 99, 5515-5520
  18. Hunt, G. and Thody, A.J. (1995) Agouti protein can act independently of melanocyte-stimulating hormone to inhibit melanogenesis. J. Endocrinol. 2, R1-4 https://doi.org/10.1677/joe.0.0020001
  19. Nakajima M, Shinoda I, Fukuwatari Y, Hayasawa H. (1998) Arbutin increases the pigmentation of cultured human melanocytes through mechanisms other than the induction of tyrosinase activity. Pigment Cell Res. 1, 12-17
  20. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. (1995) Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81, 801-809 https://doi.org/10.1016/0092-8674(95)90541-3
  21. Hirobe, T., Wakamatsu, K. and Ito, S. (2006) The slaty mutation affects eumelanin and pheomelanin synthesis in mouse melanocytes. European Journal of Cell Biology. 85, 537-549 https://doi.org/10.1016/j.ejcb.2006.01.013
  22. Martin, S.E. and Caplen, N.J. (2006) Mismatched siRNAs downregulate mRNAs as a function of target site location. FEBS Lett. 15, 3694-3698
  23. Prabhu, R., Garry, R.F. and Dash, S. (2006) Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes. Virol J. 3, 100 https://doi.org/10.1186/1743-422X-3-100
  24. Mistry, S.J., Bank, A. and Atweh, G.F. (2005) Targeting stathmin in prostate cancer. Mol Cancer Ther. 12, 1821-1829
  25. Iancu-Rubin, C., Nasrallah, C.A. and Atweh, G.F. (2005) Stathmin prevents the transition from a normal to an endomitotic cell cycle during megakaryocytic differentiation. Cell Cycle. 12, 1774-1782

Cited by

  1. Downregulation of stathmin is involved in malignant phenotype reversion and cell apoptosis in esophageal squamous cell carcinoma vol.103, pp.7, 2011, https://doi.org/10.1002/jso.21870
  2. Microtubule assembly affects bone mass by regulating both osteoblast and osteoclast functions: Stathmin deficiency produces an osteopenic phenotype in mice vol.26, pp.9, 2011, https://doi.org/10.1002/jbmr.419
  3. Proteomic Analysis of Mesenchymal Stem Cells from Normal and Deep Carious Dental Pulp vol.9, pp.5, 2014, https://doi.org/10.1371/journal.pone.0097026
  4. Neuronal stathmins: A family of phosphoproteins cooperating for neuronal development, plasticity and regeneration vol.126, 2015, https://doi.org/10.1016/j.pneurobio.2014.09.002
  5. Gene Expression Responses Linked to Reproduction Effect Concentrations (EC10,20,50,90) of Dimethoate, Atrazine and Carbendazim, in Enchytraeus albidus vol.7, pp.4, 2012, https://doi.org/10.1371/journal.pone.0036068
  6. Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection vol.5, 2014, https://doi.org/10.1038/ncomms5497
  7. Involvement of stathmin 1 in the neurotrophic effects of PACAP in PC12 cells 2010, https://doi.org/10.1111/j.1471-4159.2010.06873.x
  8. Stathmin is a potential therapeutic target but not a prognostic marker in melanoma vol.29, pp.2, 2019, https://doi.org/10.1097/CMR.0000000000000550