HSP27 inhibits cytochrome c-dependent activation of procaspase-9

被引:431
作者
Garrido, C
Bruey, JM
Fromentin, A
Hammann, A
Arrigo, AP
Solary, E
机构
[1] Fac Med & Pharm Dijon, INSERM U517, Grp Biol & Therapie Canc JE 515, F-21033 Dijon, France
[2] Univ Lyon 1, Stress Lab, CNRS UMR 5534, F-69365 Lyon, France
关键词
apoptosis; cell death; etoposide; drug resistance; leukemia;
D O I
10.1096/fasebj.13.14.2061
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
We have previously shown that the small heat shock protein HSP27 inhibited apoptotic pathways triggered by a variety of stimuli in mammalian cells. The present study demonstrates that HSP27 overexpression decreases U937 human leukemic cell sensitivity to etoposide-induced cytotoxicity by preventing apoptosis. As observed for Bcl-2, HSP27 overexpression delays poly(ADP-ribose)polymerase cleavage and procaspase-3 activation. In contrast with Bcl-2, HSP27 overexpression does not prevent etoposide-induced cytochrome c release from the mitochondria. In a cell-free system, addition of cytochrome c and dATP to cytosolic extracts from untreated cells induces the proteolytic activation of procaspase-3 in both control and bcl-2-transfected U937 cells but fails to activate procaspase-3 in HSP27-overexpressing cells. Immunodepletion of HSP27 from cytosolic extracts increases cytochrome c/dATP-mediated activation of procaspase-3. Overexpression of HSP27 also prevents procaspase-9 activation. In the cell-free system, immunodepletion of HSP27 increases LEDH-AFC peptide cleavage activity triggered by cytochrome c/dATP treatment. We conclude that HSP27 inhibits etoposide-induced apoptosis by preventing cytochrome c and dATP-triggered activity of caspase-9, downstream of cytochrome c release.-Garrido, C., Bruey, J.-M., Fromentin, A., Hammann, A,, Arrigo, A. P., Solary, E. HSP27 inhibits cytochrome c-dependent activation of procaspase-9.
引用
收藏
页码:2061 / 2070
页数:10
相关论文
共 52 条
  • [1] ARRIGO AP, 1994, HEAT SHOCK PROTEINS, P335
  • [2] CHAMPLIN R, 1987, BLOOD, V69, P1551
  • [3] Interaction of CED-4 with CED-3 and CED-9: A molecular framework for cell death
    Chinnaiyan, AM
    ORourke, K
    Lane, BR
    Dixit, VM
    [J]. SCIENCE, 1997, 275 (5303) : 1122 - 1126
  • [4] Upregulation of CASP genes in human tumor cells undergoing etoposide-induced apoptosis
    Droin, N
    Dubrez, L
    Eymin, B
    Renvoizé, C
    Bréard, J
    Dimanche-Boitrel, MT
    Solary, E
    [J]. ONCOGENE, 1998, 16 (22) : 2885 - 2894
  • [5] BCR-ABL delays apoptosis upstream of procaspase-3 activation
    Dubrez, L
    Eymin, B
    Sordet, O
    Droin, N
    Turhan, AG
    Solary, E
    [J]. BLOOD, 1998, 91 (07) : 2415 - 2422
  • [6] Pivotal role of a DEVD-sensitive step in etoposide-induced and Fas-mediated apoptotic pathways
    Dubrez, L
    Savoy, I
    Hamman, A
    Solary, E
    [J]. EMBO JOURNAL, 1996, 15 (20) : 5504 - 5512
  • [7] DUBREZ L, 1995, LEUKEMIA, V9, P1013
  • [8] Binding of non-native protein to Hsp25 during heat shock creates a reservoir of folding intermediates for reactivation
    Ehrnsperger, M
    Graber, S
    Gaestel, M
    Buchner, J
    [J]. EMBO JOURNAL, 1997, 16 (02) : 221 - 229
  • [9] Ellerby HM, 1997, J NEUROSCI, V17, P6165
  • [10] Inconstant association between 27-kDa heat-shock protein (Hsp27) content and doxorubicin resistance in human colon cancer cells - The doxorubicin-protecting effect of Hsp27
    Garrido, C
    Mehlen, P
    Fromentin, A
    Hammann, A
    Assem, M
    Arrigo, AP
    Chauffert, B
    [J]. EUROPEAN JOURNAL OF BIOCHEMISTRY, 1996, 237 (03): : 653 - 659