생명과학회지 (Journal of Life Science)

  • 제13권1호
  • /
  • Pages.118-127
  • /
  • 2003
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

Jurkat T 세포에 있어서 ρ-fluorophenylalanine에 의해 유도되는 세포자살의 Bcl-2 및 Bcl-xL에 의한 저해 기전

Ectopic expression of Bcl-2 or Bcl-xL suppresses p-fluorophenylalanine-induced apoptosis through blocking mitochondria-dependent caspase cascade in human Jurkat T cells

  • 한규현 (경북대학교 자연과학대학 미생물학과) ;
  • 오현지 (경북대학교 자연과학대학 미생물학과) ;
  • 전도연 (경북대학교 자연과학대학 미생물학과 경북대학교 자연과학대학 미생물학과) ;
  • 김영호
  • Han, Kyu-Hyun (Laboratory of Immunobiology, Department of Microbiology, College of National Sciences, Kyungpook National University) ;
  • Oh, Hyun-Ji (Laboratory of Immunobiology, Department of Microbiology, College of National Sciences, Kyungpook National University) ;
  • Jun, Do-Youn (Laboratory of Immunobiology, Department of Microbiology, College of National Sciences, Kyungpook National University) ;
  • Kim, Young-Ho (Laboratory of Immunobiology, Department of Microbiology, College of National Sciences, Kyungpook National University)
  • 발행 : 2003.02.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Phenylalanine의 구조유사체인 p-fluotophenylalanine (FPA)은 인체 급성백혈병세포주인 Jurkat T 세포의 세포자살을 유도한다. FPA에 의한 세포자살에 미치는 Bcl-2 또는 Bcl-xL의 영향을 조사하기 위해, Bcl-2 또는 Bcl-xL을 stable transfection하거나 empty vectors만을 Transfection한 Jurkat 세포를 이용하여 FPA의 세포독성과 FPA에 의한 세포내 세포자살 신호전달경로를 비교 분석하였다. Jurkt T 세포에 0.63∼3.0 mLf의 FPA를 처리하였을 때 세포의 생육도는 농도에 비례하여 감소하였다. 또한 세포자살관련 DNA fragmentation, caspase-8 activatoin, Bid cleavage, mitochondria로 부터의 cytochrome c 방출, caspase-9 및 -3 activation, PARP degradation 등이 유도되었다. 한편, FPA에 의해 유도되는 이러한 일련의 생화학적 현상들은 Bcl-2 또는 Bcl-xL의 overexpression에 의해 현저히 저해되었다. 이상의 결과들은 caspase-8 activation, Bid cleavage, mitochondnal cytochrome c 방출에 의해 활성화되는 casuase cascade 등의 현상이, Bcl-2 또는 Bcl-xL에 의해 억제됨을 나타내며 FPA에 의해 유도되는 세포자살에 필요한 과정임을 시사한다.

$\rho$-Fluorophenylalanine (FPA), a phenylalanine analog, is able to induce apoptotic cell death of human acute leukemia Jurkat T cells. To better understand the mechanism by which FPA induces apoptotic cell death, the effect of ectopic expression of antiapoptotic proteins, Bcl-2 and Bcl-xL, on FPA-induced apoptosis was investigated by employing lurkat T cells transfected with Bcl-2 gene (JT/Bcl-2) or Bcl-xL gene (1/Bcl-xL) and Jurkat T cells transfected with vector (JT/Neo or J/Neo). When Jurkat T cells, JT/Neo or J/Neo, were exposed to FPA at concentrations ranging from 0.63 to 5.0 mM, the cell viability determined by MTT assay declined in a dose-dependent manner. In addition, apoptotic DNA fragmentation along with several apoptotic events such as caspase-8 activation, Bid cleavage, mitochondrial cytochrome c release, caspase-9 activation, caspase-3 activation, and degradation of PARP was induced. However, the FPA-induced cytotoxic effect, activation of caspase-8, and cleavage of Bid were significantly abrogated by ectopic expression of Bcl-2 or Bcl-xL. At the same time, there was marked reduction in the level of cytochrome c release from mitorhondria, caspase-9 activation, caspase-3 activation, and degradation of PARP. These results indicate that caspase-8 activation, Bid cleavage, and mitochondrial cytochrome c release with subsequent activation of the caspase cascade are negatively regulated by Bcl-2 or Bcl-xL, and are thus required for FPA-induced apoptosis in Jurkat T cells

키워드

참고문헌

  1. Eur. J. Immunol. v.27 Ectopic expression of Bcl-2, but not Bcl-xL rescues Ramos B cells from Fasmediated apoptosis Alam, M. K.;S. Davison;N. Siddiqui;J. D. Norton;J. J. Murphy https://doi.org/10.1002/eji.1830271249
  2. Carcinogenesis v.23 Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl Anto, R. J. ;A. Mukhopadhyay;K. Denning;B. B. Aggarwal https://doi.org/10.1093/carcin/23.1.143
  3. Anticancer Res. v.20 Antitumor effect of L-2,4 diaminobutyric acid on a hepatoma cell line Blind, P. J.;A. Waldenstrom;D. Berggern;G. Ronquist
  4. Folia Microbiologica v.27 Variation of antimetabolite sensitivity with different carbon sources in Bacillus subtilis Chaudhuri, A.;A. K. Mishra;G. Nanda https://doi.org/10.1007/BF02879762
  5. Biochim. Biophys. Acta v.1294 Alteration in the conformational stability of collagen caused by the incorporation of the lysine analogue S-2-aminoethylcysteine Christner, P;L. Ronald;R. L. Yankowski;M. Benditt;S. A. Jimenez https://doi.org/10.1016/0167-4838(95)00261-8
  6. Cell Growth Differ. v.6 Overexpression of Bcl-XL by cytotoxic drug exposure confers resistance to ionizing radiation-induced internucleosomal DNA fragmentation Datta, R.;Y. Manome;N. Taneja;L. H. Boise;R. Weichselbaum;C. B. Thompson;C. A. Slapak;D. Kufe
  7. Mol. Cell. Biochem. v.46 Thialysineutilization by E. coli and its effects on cell growth Di Girolamo, M.;V. Busiello;C. Cini;C. Foppoli;C. De Marco https://doi.org/10.1007/BF00215580
  8. Cancer Res. v.43 Enhancement of human tumor cell killing by L-canavanine in combination with gamma radiation Green, M. H.;F. J. Ward
  9. Nucleic Acid Res. v.22 A rapid and simple method for the isolation of apoptotic DNA fragments Herrmann, M;H. M. Lorenz;R. Voll;M. Grunke;W. Woith;J. R. Kalden https://doi.org/10.1093/nar/22.24.5506
  10. Biochem. Biophys. Res.Commun. v.295 Arginine antimetabolite L-canavanine induces apoptotic cell death in human Jukat T cells via caspase-3 activation regulated by Bcl-2 Bcl-xL Jang, M. H.;D. Y. Jun;S. W. Rue;K. H. Han;W. Park;Y. H. Kim https://doi.org/10.1016/S0006-291X(02)00650-2
  11. J. Immunol. v.149 Expression of the murine homologue of the cell cycle control protein p34cdc2 in T lymphocytes Kim, Y. H.;J. J. Proust;M. J. Buchholz;F. J. Chrest;A. A. Nordin
  12. Science v.275 The release of cytochrome c from mitochondria: a primany site for Bcl-2 regulation of apoptosis Kluck, R. M.;E. Bossy-Wetzel;D. R. Green;D. D. Newmeyer https://doi.org/10.1126/science.275.5303.1132
  13. Nature v.371 Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE Lazebnik, Y. A.;S. H. Kaufmann;S. Desnoyers;G. G. Poirer;W. C. Earnshaw https://doi.org/10.1038/371346a0
  14. J. Gen. Virol. v.65 Reversible inhibition of bovine parvovirus DNA replication by aphidicolin and L-canavanine Robertson, A. T.;R.C. Bates;E. R. Stout https://doi.org/10.1099/0022-1317-65-9-1497
  15. Israel J. Plant Sci. v.45 Inhibition of polyamine biosynthesis by L-canavanine and its effect of meristematic activity, growth, and development of Zea mays roots Schwartz, M.;A. Altman;Y. Cohen;T. Arzee https://doi.org/10.1080/07929978.1997.10676666
  16. Nature v.374 Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL Shimizu, S.;Y. Eguchi;H. Kosaka;W. Kamiike;H. Matsuda;Y. Tsujimoto https://doi.org/10.1038/374811a0
  17. Blood v.90 Bcl-2 and Bcl-xL can differentially block chemotherapy-induced cell death Simonian, P. L.;D. A. Grillot;G. Nunez
  18. Genetika v.37 Lysine overproduction mutations in the yeast Saccharomyces cerevisiae and its transfection into industrial Yeast strains Stepanova, V. P.;S. G. Davydenko;V. N. Donich;S. S. Smolina;O. N. Kurennaia;B. F. Iarovo
  19. Anticancer Drugs v.6 Combination therapy with 5-fluoruracil and L-canavanine: in vitro and in vivo studies Swaffar, D. S.;C, Y, Ang;P. B. Desai;G. A. Rosenthal;D. A. Thmas;P. A. Crooks;W. J. John https://doi.org/10.1097/00001813-199508000-00012
  20. Cancer Res. v.46 Growth inhibition of a rat colon tumor by L-canavanine Thomas, D. A.;G. A. Rosenthal;D. V. Gold;K. M. Dickey
  21. Cell Death Differ. v.7 Sausville, Susceptibility to druginduced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels Tudor, G.;A. Aguilera;D. O. Halverson;N. D. Laing;E. A. https://doi.org/10.1038/sj.cdd.4400688
  22. Science v.275 Pervention of apoptosis by Bcl-2; release of cytochrome c from metochondria blocked Yang, J.;X. Lin;K. Bhalla;C. N. Kim;A. M. Ibrado;J. Cai;T. I. Peng;D. P. Jones;X. Wang https://doi.org/10.1126/science.275.5303.1129
  23. Curr. Opin. Invest. Drugs v.2 Alanosine Yu, J.
  24. J. Gen. Microbiol. v.122 Genetic and biochemical properties fo thialysine-resistant mutants of Saccharomyces cerevisiae Zwolshen, J. H.;J. K. Bhattacharjee