Susceptibility of HIV-1-TAT transfected cells to undergo apoptosis.: Biochemical mechanisms

被引:60
作者
Macho, A [1 ]
Calzado, MA [1 ]
Jiménez-Reina, L [1 ]
Ceballos, E [1 ]
León, J [1 ]
Muñoz, E [1 ]
机构
[1] Univ Cordoba, Fac Med, Dept Fisiol & Inmunol, E-14071 Cordoba, Spain
关键词
Tat; apoptosis; Bcr-abl; CPP32; mitochondria;
D O I
10.1038/sj.onc.1203095
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of HIV-1 Tat protein on mitochondria membrane permeability and apoptosis were analysed in lymphoid cells. In this report we show that stable-transfected HIV-Tat cells are primed to undergo apoptosis upon serum withdrawal. This effect was observed in both the Jhan T cell line and the K562 cells, the latter expressing the bcr-abl chimeric gene, which confers resistance to apoptosis induced by different stimuli. Using a cytofluorimetric approach we have determined that serum withdrawal induces a disruption of the transmembrane mitochondrial potential (Delta psi(m)) followed bq an increase of reactive oxygen species (ROS) and the subsequent DNA nuclear loss in K562-Tat cells but not in the K562-pcDNA cell line. These pre-apoptotic events were associated with the cleavage of the caspase-3, while the expression of Bcl-2, Bcl-X-L and Bas proteins was not affected by the presence of Tat, Regardless of the steady state of the Bar protein, we found that in both K562 and K562-Tat cells, this protein is located in the nucleus, but after serum withdrawal its localization was mainly in the cytoplasm, The activity of caspase-3 detected in K562-Tat cells after serum withdrawal paralleled with the mitochondria permeability transition. Nevertheless, in Jhan-Tat cells the inhibition of this caspase with the specific inhibitor, z-DEVD-cmk, did not affect the disruption of the mitochondria potential induced by serum withdrawal. Interestingly, ae found that HIV-Tat protein accumulates at the mitochondria in the K562-Tat cells cultured under low serum conditions, and this mitochondrial localization correlated with the Delta psi(m) disruption detected in these cells. In addition, HIV-Tat protein synergies with protoporphyrin IX (PPIX), a ligand of the mitochondrial benzodiazepine receptor, in the induction of apoptosis in both Jhan and K562 cells. Thus, HIV-1 Tat protein may induce apoptosis by a mechanism that involves mitochondrial PT and may contribute to the lymphocyte depletion seen in AIDS patients.
引用
收藏
页码:7543 / 7551
页数:9
相关论文
共 66 条
[51]   The central executioner of apoptosis: Multiple connections between protease activation and mitochondria in Fas/APO-1/CD95- and ceramide-induced apoptosis [J].
Susin, SA ;
Zamzami, N ;
Castedo, M ;
Daugas, E ;
Wang, HG ;
Geley, S ;
Fassy, F ;
Reed, JC ;
Kroemer, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) :25-37
[52]   Bcl-2 inhibits the mitochondrial release of an apoptogenic protease [J].
Susin, SA ;
Zamzami, N ;
Castedo, M ;
Hirsch, T ;
Marchetti, P ;
Macho, A ;
Daugas, E ;
Geuskens, M ;
Kroemer, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (04) :1331-1341
[53]   Caspases: Enemies within [J].
Thornberry, NA ;
Lazebnik, Y .
SCIENCE, 1998, 281 (5381) :1312-1316
[54]   DIFFERENTIAL SUSCEPTIBILITY TO MONOMERIC HIV GP120-MEDIATED APOPTOSIS IN ANTIGEN-ACTIVATED CD4(+) T-CELL POPULATIONS [J].
Tuosto, L ;
Gilardini Montani, MS ;
Lorenzetti, S ;
Cundari, E ;
Moretti, S ;
Lombardi, G ;
Piccolella, E .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (10) :2907-2916
[55]  
Wadia JS, 1998, J NEUROSCI, V18, P932
[56]   Bcl-2 targets the protein kinase Raf-1 to mitochondria [J].
Wang, HG ;
Rapp, UR ;
Reed, JC .
CELL, 1996, 87 (04) :629-638
[57]   VIRAL DYNAMICS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION [J].
WEI, XP ;
GHOSH, SK ;
TAYLOR, ME ;
JOHNSON, VA ;
EMINI, EA ;
DEUTSCH, P ;
LIFSON, JD ;
BONHOEFFER, S ;
NOWAK, MA ;
HAHN, BH ;
SAAG, MS ;
SHAW, GM .
NATURE, 1995, 373 (6510) :117-122
[58]   SENSITIZATION OF T-CELLS TO CD95-MEDIATED APOPTOSIS BY HIV-1 TAT AND GP120 [J].
WESTENDORP, MO ;
FRANK, R ;
OCHSENBAUER, C ;
STRICKER, K ;
DHEIN, J ;
WALCZAK, H ;
DEBATIN, KM ;
KRAMMER, PH .
NATURE, 1995, 375 (6531) :497-500
[59]   HIV-1 TAT POTENTIATES TNF-INDUCED NF-KAPPA-B ACTIVATION AND CYTOTOXICITY BY ALTERING THE CELLULAR REDOX STATE [J].
WESTENDORP, MO ;
SHATROV, VA ;
SCHULZEOSTHOFF, K ;
FRANK, R ;
KRAFT, M ;
LOS, M ;
KRAMMER, PH ;
DROGE, W ;
LEHMANN, V .
EMBO JOURNAL, 1995, 14 (03) :546-554
[60]   Movement of Bax from the cytosol to mitochondria during apoptosis [J].
Wolter, KG ;
Hsu, YT ;
Smith, CL ;
Nechushtan, A ;
Xi, XG ;
Youle, RJ .
JOURNAL OF CELL BIOLOGY, 1997, 139 (05) :1281-1292