Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Regulation of Phospholipase D by CoCl2 in Human Glioblastoma Cells

인간 교세포주에서 CoCl2에 의한 phospholipase D의 조절기전

  • Lee, Seung-Hoon (Department of Molecular Biology, Pusan National University) ;
  • Min, Gye-Sik (Department of Microbiological Engineering, Jinju National University) ;
  • Min, Do-Sik (Department of Molecular Biology, Pusan National University)
  • 이승훈 (부산대학교 자연과학대학 분자생물학과) ;
  • 민계식 (진주산업대학교 미생물공학과) ;
  • 민도식 (부산대학교 자연과학대학 분자생물학과)
  • Published : 2006.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Phospholipase D (PLD) is known to play an important role in a variety of cells. However, little is known about $CoCl_2-mediated$ PLD signaling. In this study we demonstrated for the first time that $CoCl_2$ stimulates PLD activity and increases expression of cyclooxygenase-2 (COX-2), which is known to mediate inflammatory reaction. $CoCl_2-induced$ PLD activity was assessed by measuring the formation of $[^3H]$ phosphatidylbutanol (PtdBut), the product of PLD-mediated transphosphatidylation, in the presence of 1-butanol. To study mechanism of PLD signaling induced by $CoCl_2$, U87 human glioblastoma cells were stimulated by $CoCl_2$ and regulators of PLD activity induced by $CoCl_2$ were investigated using several inhibitors of signaling proteins. Moreover, PLD activation by $CoCl_2$ increased not only expression of COX-2 protein but also COX-2 promoter activity. In summary, these results suggest that $CoCl_2$ increases expression of COX-2 protein via PLD in human U87 glioblastoma cells.

본 연구에서 최근 세포내 신호전달을 매개하는 중요한 효소로써 PLD 동위효소에 대하여, $CoCl_2$가 PLD 동위효소의 활성을 증가시킨다는 사실을 밝혔으며, 중간에 매개되는 단백질로써, PLD1은 p38 MAP kinase, PKA와 $PKC-{\delta}$의 조절을 받고 PLD2는 p38 MAP kinase와 PLC의 조절을 받으므로 그 활성 기전이 각각 다르다는 사실을 확인하였다. 그리고 $CoCl_2$에 의해 생성되는 활성산소 종에 의한 염증상태가 유도될 것이라고 예상하였고 $CoCl_2$가 PLD 동위효소를 매개로 하여 염증상태에서만 특이적으로 발현되고 염증반응을 매개하는 COX-2 단백질에 어떠한 영향을 미칠 것인가를 조사하였다. 결과적으로 $CoCl_2$에 의해 PLD 효소 활성이 증가됨으로써 COX-2의 발현이 증가한다는 것을 발견하였을 뿐만 아니라 COX-2의 발현에 대하여 COX-2 promoter의 활성도 증가한다는 사실을 확인함으로써 전사수준에서의 결과도 이를 뒷받침 해 주고 있었다.

Keywords

References

  1. Atlante, A., S. G. M. Gagliardi, M. T. Minervini, E. Ciotti, and M. P. Calissano. 1997. Glutamate neurotoxicity in rat cerebellar granule cells: a major role for xanthine oxidase in oxygen radical formation. J. Neurochem. 68, 2038-2045 https://doi.org/10.1046/j.1471-4159.1997.68052038.x
  2. Bae, Y. S., Y. Kim, J. H. Kim, T. G. Lee, P. G. Suh and S. H. Ryu. 2000. Independent functioning of cytosolic phospholipase A2 and phospholipase D1 in Trp-Lys-Tyr-Met- Val-D-Met-induced superoxide generation in human monocytes. J. Immunol. 164, 4089-4096 https://doi.org/10.4049/jimmunol.164.8.4089
  3. Balboa, M. A., J. Balsinde and E. A. Dennis. 1998. Involvement of phosphatidate phosphohydrolase in arachidonic acid mobilization in human amnionic WISH cells. J. Biol. Chem. 273, 7684-7690 https://doi.org/10.1074/jbc.273.13.7684
  4. Bronstein, D. M., I. Perez-Otano, V. Sun, S. B. Mullis Sawin, J. Chan, G. C. Wu, P. M. Hudson, L. Y. Kong, J. S. Hong and M. K. McMillian. 1995. Glia-dependent neurotoxicity and neuroprotection in mesencephalic cultures. Brain Res. 704, 112-116 https://doi.org/10.1016/0006-8993(95)01189-7
  5. Brown, J. M. 2000. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol. Med. Today 4, 157-162
  6. Crofford, L. J. 1997. COX-1 and COX-2 tissue expression: implications and predictions. J. Rheumatol. 49, 15-19
  7. Cummings, R. J., N. L. Parinandi, A. Zaiman, L. Wang, P. V. Usatyuk, J. G. Garcia and V. Natarajan. 2002. Phospholipase D activation by sphingosine 1-phosphate regulates interleukin-8 secretion in human bronchial epithelial cells. J. Biol. Chem. 277, 30227-30235 https://doi.org/10.1074/jbc.M111078200
  8. Czarny, M., Y. Lavie, G. Fiucci and M. Liscovitch. 1999. Localization of Phospholipase D in Detergent-insoluble, Caveolin-rich Membrane Domains. J. Biol. Chem. 274, 2717-2724 https://doi.org/10.1074/jbc.274.5.2717
  9. DeWitt, D. and W. Smith. 1988. Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence. Proc. Natl. Acad. Sci. USA 85, 1412-1416
  10. Exton, J. H. 1994. Phosphatidylcholine breakdown and signal transduction. Biochim. Biophys. Acta. 1212, 26-42 https://doi.org/10.1016/0005-2760(94)90186-4
  11. Exton, J. H. 1999. Regulation of phospholipase D. Biochim. Biophys. Acta. 1439, 121-33 https://doi.org/10.1016/S1388-1981(99)00089-X
  12. Floyd, R. A. 1990. Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J. 4, 2587-2597 https://doi.org/10.1096/fasebj.4.9.2189775
  13. Freyberg, Z., D. Sweeney, A. Siddhanta, S. Bourgoin, M. Frohman and D. Shields. 2001. Intracellular localization of phospholipase D1 in mammalian cells. Mol. Biol. Cell 12, 943-955 https://doi.org/10.1091/mbc.12.4.943
  14. Fujita, K., M. Murakami, F. Yamashita, K. Amemiya and I. Kudo. 1996. Phospholipase D is involved in cytosolic phospholipase A2-dependent selective release of arachidonic acid by fMLP-stimulated rat neutrophils. FEBS Lett. 395, 293-298 https://doi.org/10.1016/0014-5793(96)01056-3
  15. Guichun, W., K. H. Tapas, M. Sankar, L. Heung-Man and W. E. Ella. 2000. Mitochondria DNA damage and a hypoxic response are induced by $CoCl_2$ in rat neuronal PC12 cells. Nucleic Acids Res. 28, 2135-2140 https://doi.org/10.1093/nar/28.10.2135
  16. Guillemin, K. and M. A. Krasnow. 1997. The hypoxic response: huffing and HIFing. Cell 89, 9-12 https://doi.org/10.1016/S0092-8674(00)80176-2
  17. Hammond, S. M., J. M. Jenco, S. Nakashima, K. Cadwallader, Q. Gu, S. Cook, Y. Nozawa, G. D. Prestwich, M. A. Frohman and A. J. Morris. 1997. Characterization of two alternately spliced forms of phospholipase D1. Activation of the purified enzymes by phosphatidylinositol 4,5-bisphosphate, ADP-ribosylation factor, and Rho family monomeric GTP-binding proteins and protein kinase C. J. Biol. Chem. 272, 3860-3868 https://doi.org/10.1074/jbc.272.6.3860
  18. Hammond, S. M., Y. M. Altshuller, T. C. Sung, S. A. Rudge, K. Ross, J. Engebrecht, A. J. Morris and M. A. Frohman. 1995. Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family. J. Biol. Chem. 270, 29640-29643 https://doi.org/10.1074/jbc.270.50.29640
  19. Hla, T. and T. Maciag. 1991. Cyclooxygenase gene expression is down-regulated by heparin-binding (acidic fibroblast) growth factor-1 in human endothelial cells. J. Biol. Chem. 266, 24059-24063
  20. Hoozemans, J. J., A. J. Rozemuller, I. Janssen, C. J. De Groot, R. Veerhuis and P. Eikelenboom. 2001. Cyclooxygenase expression in microglia and neurons in Alzheimer's disease and control brain. Acta. Neuropathol. 101, 2-8
  21. Huot, J., F. Houle, F. Marceau and J. Landr. 1997. Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ. Res. 80, 383-392 https://doi.org/10.1161/01.RES.80.3.383
  22. Kanaya, K. and T. Kamitani. 2003. pVHL-independent ubiquitination of $HIF1{\alpha}$ and its stabilization by cobalt ion. Biochem. Biophys. Res. Commun. 306, 750-755 https://doi.org/10.1016/S0006-291X(03)01041-6
  23. Kim, J. H., B. D. Lee, Y. Kim, S. D. Lee, P. G. Suh and S. H. Ryu. 1999. Cytosolic phospholipase A2-mediated regulation of phospholipase D2 in leukocyte cell lines. J. Immunol. 163, 5462-5470
  24. Kim, Y., J. M. Han, B. R. Han, K. A. Lee, J. H. Kim, B. D. Lee, I. H. Jang, P. G. Suh and S. H. Ryu. 2000. Phospholipase D1 Is Phosphorylated and Activated by Protein Kinase C in Caveolin-enriched Microdomains within the Plasma Membrane. J. Biol. Chem. 18, 13621-13627
  25. Lal, M. A., H. Brismar, A. C. Eklof and A. Aperia. 2002. Role of oxidative stress in advanced glycation end product- induced mesangial cell activation. Kidney Int. 61, 2006-2014 https://doi.org/10.1046/j.1523-1755.2002.00367.x
  26. Lancelot, E., J. Callebert, M. L. Revaud, R. G. Boulu and M. Plotkine. 1995. Detection of hydroxyl radicals in rat striatum during transient focal cerebral ischemia: possible implication in tissue damage. Neurosci. Lett. 197, 85-88 https://doi.org/10.1016/0304-3940(95)11901-8
  27. Lee, M. Y., S. Y. Kim, D. S. Min, Y. S. Choi, S. L. Shin, M. H. Chun, S. B. Lee, M. S. Kim and Y. H. Jo. 2000. Upregulation of phospholipase D in astrocytes in response to transient forebrain ischemia. Glia 30, 311-317 https://doi.org/10.1002/(SICI)1098-1136(200005)30:3<311::AID-GLIA10>3.0.CO;2-K
  28. Lin, L. L., M. Wartmann, A. Y. Lin, J. L. Knopf, A. Seth and R. J. Davis. 1993. cPLA2 is phosphorylated and activated by MAP kinase. Cell 72, 269-278 https://doi.org/10.1016/0092-8674(93)90666-E
  29. Liscovitch, M., M. Czarny, G. Fiucci and X. Tang. 2000. Phospholipase D: molecular and cell biology of a novel gene family. Biochem. J. 345, 401-415 https://doi.org/10.1042/0264-6021:3450401
  30. Liu, B. and J. S. Hong. 2003. Role of microglia in inflammation mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J. Pharmacol. Exp. Ther. 304, 1-7 https://doi.org/10.1124/jpet.102.035048
  31. McGeer, P. L., S. Itagaki, B. E. Boyes and E. G. McGeer. 1988. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38, 1285-1291 https://doi.org/10.1212/WNL.38.8.1285
  32. Merrill, J. E., Y. Koyanagi, J. Zack, L. Thomas, F. Martin and I. S. Chen. 1992. Induction of interleukin-1 and tumor necrosis factor alpha in brain cultures by human immunodeficiency virus type1. J. Virol. 66, 2217-2225
  33. Minghetti, L. and G. Levi. 1998. Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog. Neurobiol. 54, 99 -125 https://doi.org/10.1016/S0301-0082(97)00052-X
  34. Murakami, M., T. Kambe, S. Shimbara and I. Kudo. 1999. Functional Coupling Between Various Phospholipase A2s and Cyclooxygenases in Immediate and Delayed Prostanoid Biosynthetic Pathways. J. Biol. Chem. 274, 3103-3115 https://doi.org/10.1074/jbc.274.5.3103
  35. Murakami, M., S. Shimbara, T. Kambe, H. Kuwata, M. V. Winstead, J. A. Tischfield and I. Kudo. 1998. The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release. J. Biol. Chem. 273, 14411-14423 https://doi.org/10.1074/jbc.273.23.14411
  36. Park, S. K., J. P. Provost, C. D. Bae, W. T. Ho and J. H. Exton. 1997. Cloning and characterization of phospholipase D from rat brain. J. Biol. Chem. 272, 29268-29271
  37. Pasinetti, G. M. and P. S. Aisen. 1998. Cyclooxygenase-2 expression is increased in frontal cortex of Alzheimer's disease brain. Neuroscience 87, 319-324 https://doi.org/10.1016/S0306-4522(98)00218-8
  38. Raine, C. S. 1994. Multiple sclerosis: immune system molecule expression in the central nervous system. J. Neuropathol. Exp. Neurol. 53, 328-337 https://doi.org/10.1097/00005072-199407000-00002
  39. Rosenberger, J., G. Petrovics and B. Buzas. 2001. Oxidative stress induces proorphanin FQ and proenkephalin gene expression in astrocytes through p38- and ERK-MAP kinases and NF-kappaB. J. Neurochem. 79, 35-44 https://doi.org/10.1046/j.1471-4159.2001.00520.x
  40. Rukenstein, A., R. E. Rydel and L. A. Greene. 1991. Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription independent mechanisms. J. Neurosci. 11, 2552-2563 https://doi.org/10.1523/JNEUROSCI.11-08-02552.1991
  41. Shimizu, S., Y. Eguchi, W. Kamiike, H. Matsuda and Y. Tsujimoto. 1996. Bcl-2 expression prevents activation of the ICE protease cascade. Oncogene 12, 2251-2257
  42. Simonson, S. G., J. Zhang, A. T. Jr. Canada, Y. F. Su, H. Benveniste and C. A. Piantadosi. 1993. Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain. J. Cereb. Blood Flow Metab. 13, 125-134 https://doi.org/10.1038/jcbfm.1993.15
  43. Sung, T. C., Y. Zhang, A. J. Morris and M. A. Frohman. 1999. Structural Analysis of Human Phospholipase D1. J. Biol. Chem. 274, 3659-3666 https://doi.org/10.1074/jbc.274.6.3659
  44. Tao, J., J. S. Sanghera, S. L. Pelech, G. Wong and J. G. Levy. 1996. Stimulation of stress-activated protein kinase and p38 HOG1 kinase in murine keratinocytes following photodynamic therapy with benzoporphyrin derivative. J. Biol. Chem. 271, 27107-27115 https://doi.org/10.1074/jbc.271.43.27107
  45. Ushio-Fukai, M., R. W. Alexander, M. Akers and K. K. Griendling. 1998. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signalling pathways activated by angiotensinII. Role in vascular smooth muscle cell hypertrophy. J. Biol. Chem. 273, 15022-15029 https://doi.org/10.1074/jbc.273.24.15022
  46. Yamazaki, M., Y. Zhang, H. Watanabe, T. Yokozeki, S. Ohno, K. Kaibuchi, H. Shibata, H. Muraki, Y. Ono, M. A. Frohman and Y. Kanaho. 1999. Interaction of the small G protein RhoA with the C Terminus of human Phospholipase D1. J. Biol. Chem. 274, 6035-6038 https://doi.org/10.1074/jbc.274.10.6035
  47. Zhong, M., T. Joseph, D. Jackson, S. Beychenok and D. A. Foster. 2002. Elevated phospholipase D activity induces apoptosis in normal rat fibroblasts. Biochem. Biophys. Res. Commun. 298, 474-477 https://doi.org/10.1016/S0006-291X(02)02495-6