통합자연과학논문집 (Journal of Integrative Natural Science)

조선대학교 기초과학연구원 (The Basic Science Institute Chosun University)
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세포 이동에서 PI3K 억제제인 LY294002의 효과

Effect of a PI3K inhibitor LY294002 on cell migration

  • 김원범 (조선대학교 글로벌바이오융합학과, BK21 FOUR 노인성 질환 제어 기술 교육 연구단) ;
  • 전택중 (조선대학교 글로벌바이오융합학과, BK21 FOUR 노인성 질환 제어 기술 교육 연구단)
  • Kim, Wonbum (Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-associated Disorder Control Technology, Chosun University) ;
  • Jeon, Taeck Joong (Department of Integrative Biological Sciences & BK21 FOUR Educational Research Group for Age-associated Disorder Control Technology, Chosun University)
  • 투고 : 2022.09.26
  • 심사 : 2022.09.29
  • 발행 : 2022.10.14
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초록

Cell migration is essential for diverse cellular processes including wound healing, immune response, development, and cancer metastasis. Pi3-kinase (PI3K) is a key regulator for actin cytoskeleton and phosphorylates phosphatidylinositol (4,5)-diphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3). High levels of PIP3 by PI3Ks are associated with increased levels of F-actin and pseudopod extension at the leading edge of migrating cells such as neutrophils and Dictyostelium. LY294002 is a well-known PI3K specific inhibitor. Here, we investigated the effect of LY294002 on cell migration. First, we evaluated the appropriate concentration of dimethyl sulfoxide (DMSO) for using as a solvent for LY294002. DMSO is a highly polar organic reagent and one of the most common solvent for organic and inorganic chemicals. Cell morphology and cell migration were unaffected at the concentrations less than 0.1 % DMSO. Therefore, stock solution of LY294002 was prepared so that the final concentration of DMSO was 0.1 % or less when treated. When cells were treated with LY294002, cell migration was increased in a concentration-dependent manner. The maximum speed was detected in the presence of 30 µM LY294002. These results suggest that PI3Ks play a inhibitory role in regulating cell migration in our experimental conditions.

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참고문헌

  1. Jin T, Xu X, Fang J, Isik N, Yan J, Brzostowski JA, Hereld D. How human leukocytes track down and destroy pathogens: lessons learned from the model organism Dictyostelium discoideum. Immunol Res, Vol. 43, (1-3) pp. 118-27, 2009. https://doi.org/10.1007/s12026-008-8056-7
  2. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR. Cell migration: integrating signals from front to back. Science. Vol. 302, pp 1704-1709, 2003. https://doi.org/10.1126/science.1092053
  3. Chisholm RL, Firtel RA. Insights into morphogenesis from a simple developmental system. Nat Rev Mol Cell Biol. Vol. 5, pp. 531. 2004 https://doi.org/10.1038/nrm1427
  4. Lee MR, Jeon TJ. Cell migration: regulation of cytoskeleton by Rap1 in Dictyostelium discoideum. J Microbiol. Vol. 50, pp. 555-561. 2012 https://doi.org/10.1007/s12275-012-2246-7
  5. Zhang, P., Y. Wang, H. Sesaki, and M. Iijima. Proteomic identification of phosphatidylinositol (3,4,5) triphosphate - binding proteins in Dictyostelium discoideum. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A. Vol. Jun 29;107(26) pp. 11829-34. 2010. https://doi.org/10.1073/pnas.1006153107
  6. Merlot S, Firtel RA. Leading the way: Directional sensing through phosphatidylinositol 3-kinase and other signaling pathways. J Cell Sci. Vol. Sep 1;116(Pt 17) pp. 3471-8. 2003 https://doi.org/10.1242/jcs.00703
  7. Kortholt A, van Haastert PJ. Highlighting the role of Ras and Rap during Dictyostelium chemotaxis. Cell Signal. Vol. Aug;20(8) pp. 1415-22. 2008 https://doi.org/10.1016/j.cellsig.2008.02.006
  8. Sasaki AT, Firtel RA. Regulation of chemotaxis by the orchestrated activation of Ras, PI3K, and TOR. Eur J Cell Biol. Vol. Sep;85(9-10) pp. 873-95. .2006 https://doi.org/10.1016/j.ejcb.2006.04.007
  9. Yumura S, Fukui Y. Filopodelike projectionsinduced with dimethyl sulfoxide and their relevance to cellular polarity in Dictyostelium. J Cell Biol. Vol. Mar;96(3) pp. 857-65. 1983 https://doi.org/10.1083/jcb.96.3.857
  10. Litschko C, Damiano-Guercio J, BruhmannS, Faix J. Analysis of Random Migration of Dictyostelium Amoeba in Confined and Unconfined Environments. Methods Mol Biol. Vol. 1749 pp. 341-350. 2018 https://doi.org/10.1007/978-1-4939-7701-7_24
  11. Gao R, Zhao S, Jiang X, Sun Y, Zhao S, Gao J, Borleis J, Willard S, Tang M, Cai H, Kamimura Y, Huang Y, Jiang J, Huang Z, Mogilner A, Pan T, Devreotes PN, Zhao M. A large-scale screen reveals genesthat mediate electrotaxis in Dictyostelium discoideum. Sci Signal. Vol. May 26;8(378): ra50. 2015 https://doi.org/10.1126/scisignal.aab0562
  12. Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R, Balla T, Yamazaki M, Watanabe H, Itoh R, Kuroda S, Horie Y, Forster I, Mak TW, Yonekawa H, Penninger JM, Kanaho Y, Suzuki A, Sasaki T. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol. Vol. Jan;9(1) pp 36-44. 2007 https://doi.org/10.1038/ncb1515
  13. Chisholm, R.L., and Firtel, R.A. Insights into morphogenesis from a simple developmental system. Vol. 5, pp. 531. 2004
  14. Lam RS, Shumilina E, Matzner N, ZemtsovaIM, Sobiesiak M, Lang C, Felder E, Dietl P, Huber SM, Lang F. Phosphatidylinositol-3-kinase regulates mast cell ion channel activity. Cell Physiol Biochem. Vol. 22(1-4) pp. 169-76. 2004 https://doi.org/10.1159/000149794
  15. Nauc V, De Lamirande E, Leclerc P, Gagnon C. Inhibitors of phosphoinositide 3-kinase, LY294002 and wortmannin, affect sperm capacitation and associated phosphorylation of proteins differently: Ca2+-dependent divergences. J Androl. Vol. Jul-Aug;25(4) pp. 573-85. 2004 https://doi.org/10.1002/j.1939-4640.2004.tb02828.x
  16. Sun H, Oudit GY, Ramirez RJ, Costantini D, Backx PH. The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte contractility via a direct inhibition of Ik,slow currents. Cardiovasc Res. Vol. Jun 1;62(3) pp. 509-20. 2004 https://doi.org/10.1016/j.cardiores.2004.01.029