Role of c-Jun N-terminal kinase/p38 stress signaling in 1-β-D-arabinofuranosylcytosine-induced apoptosis

被引:24
作者
Stadheim, TA [1 ]
Saluta, GR [1 ]
Kucera, GL [1 ]
机构
[1] Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA
关键词
p38; JNK; SAPK; ERK; 1-beta-D-arabinofuranosylcytosine; apoptosis; PD098059; SB203580;
D O I
10.1016/S0006-2952(99)00330-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1-beta-D-Arabinofuranosylcytosine (ara-C) induced apoptosis in HL-60 cells, which was preceded by the activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), and p38 mitogen-activated protein kinase (MAPK). 2'-Amino-3'-methoxyflavone (PD098059) and 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) were used to inhibit the activity of ERK and p38, respectively. SEK-AL, a dominant-negative mutant of SEK1, was transfected into HL-60 cells (HL-60/SEK-AL) to assess the role of JNK/SAPK activity in apoptosis. PD098059 (25 mu M) inhibited ara-C-induced caspase-3-like activity but was ineffective in altering ara-C-mediated apoptotic DNA fragmentation and clonogenicity. On the other hand, SB203580 (20 mu M) inhibited ara-C-induced caspase-3-like activity, apoptotic DNA fragmentation, and clonogenicity. The inhibition of JNK1 activation in HL-60/SEK-AL cells did not block ara-C-induced apoptotic DNA fragmentation. These results suggest that ara-C-induced apoptotic DNA fragmentation and loss of clonogenicity occur through a p38-dependent pathway. BIOCHEM PHARMACOL 59;4:407-418, 2000. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:407 / 418
页数:12
相关论文
共 40 条
[1]   The activation of p38 and apoptosis by the inhibition of ERK is antagonized by the phosphoinositide S-kinase/Akt pathway [J].
Berra, E ;
Diaz-Meco, MT ;
Moscat, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (17) :10792-10797
[2]   ALTERATION OF THE PHARMACOKINETICS OF HIGH-DOSE ARA-C BY ITS METABOLITE, HIGH ARA-U IN PATIENTS WITH ACUTE-LEUKEMIA [J].
CAPIZZI, RL ;
YANG, JL ;
CHENG, E ;
BJORNSSON, T ;
SAHASRABUDHE, D ;
TAN, RS ;
CHENG, YC .
JOURNAL OF CLINICAL ONCOLOGY, 1983, 1 (12) :763-771
[3]   The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation - Duration of JNK activation may determine cell death and proliferation [J].
Chen, YR ;
Wang, XP ;
Templeton, D ;
Davis, RJ ;
Tan, TH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (50) :31929-31936
[4]   SB-203580 IS A SPECIFIC INHIBITOR OF A MAP KINASE HOMOLOG WHICH IS STIMULATED BY CELLULAR STRESSES AND INTERLEUKIN-1 [J].
CUENDA, A ;
ROUSE, J ;
DOZA, YN ;
MEIER, R ;
COHEN, P ;
GALLAGHER, TF ;
YOUNG, PR ;
LEE, JC .
FEBS LETTERS, 1995, 364 (02) :229-233
[5]   Activation of the CPP32 protease in apoptosis induced by 1-beta-D-arabinofuranosylcytosine and other DNA-damaging agents [J].
Datta, R ;
Banach, D ;
Kojima, H ;
Talanian, RV ;
Alnemri, ES ;
Wong, WW ;
Kufe, DW .
BLOOD, 1996, 88 (06) :1936-1943
[6]   A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD [J].
Enari, M ;
Sakahira, H ;
Yokoyama, H ;
Okawa, K ;
Iwamatsu, A ;
Nagata, S .
NATURE, 1998, 391 (6662) :43-50
[7]   Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6 [J].
Enslen, H ;
Raingeaud, J ;
Davis, RJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (03) :1741-1748
[8]  
FRAM RJ, 1982, CANCER RES, V42, P4050
[9]   p38 mitogen-activated protein kinase-dependent and -independent intracellular signal transduction pathways leading to apoptosis in human neutrophils [J].
Frasch, SC ;
Nick, JA ;
Fadok, VA ;
Bratton, DL ;
Worthen, GS ;
Henson, PM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (14) :8389-8397
[10]  
Grant S, 1996, CELL GROWTH DIFFER, V7, P603