Caspase-1 activation of caspase-6 in human apoptotic neurons

被引:70
作者
Guo, H
Pétrin, D
Zhang, Y
Bergeron, C
Goodyer, CG
LeBlanc, AC
机构
[1] Sir Mortimer B Davis Jewish Hosp, Bloomfield Ctr Res Aging, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada
[2] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada
[3] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 3H2, Canada
[4] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada
[5] McGill Univ, Dept Pediat, Montreal, PQ H3H 1P3, Canada
关键词
caspase-6; caspase-1; primary human neurons; apoptosis; cell death;
D O I
10.1038/sj.cdd.4401753
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
Active caspase-6 (Csp-6) induces cell death in primary cultures of human neurons and is abundant in the neuropathological lesions of Alzheimer's disease. However, the mode of Csp-6 activation is not known. Here, we show that the Csp-1 inhibitor, Z-YVAD-fmk specifically prevents activation of Csp-6 and cell death in human neurons. A transient increase in Csp-1-like activity and an increase in the p23Csp-1 subunit occur early after serum deprivation. Recombinant active Csp-1 (R-Csp-1) cleaves recombinant and neuronal pro-Csp-6 in vitro resulting in Csp-6 activity. However, R-Csp-1 does not induce cell death when microinjected in human neurons despite the inhibition of serum-deprivation induced cell death with a Csp-1 dominant negative construct. These results show that Csp-1 is an upstream positive regulator of Csp-6-mediated cell death in primary human neurons. Furthermore, these results suggest that the activation of Csp-1 must be accompanied by an apoptotic insult to induce Csp-6-mediated cell death.
引用
收藏
页码:285 / 292
页数:8
相关论文
共 40 条
[1]  
Alvarez X A, 1997, Ann N Y Acad Sci, V826, P375, DOI 10.1111/j.1749-6632.1997.tb48486.x
[2]   A unified model for apical caspase activation [J].
Boatright, KM ;
Renatus, M ;
Scott, FL ;
Sperandio, S ;
Shin, H ;
Pedersen, IM ;
Ricci, JE ;
Edris, WA ;
Sutherlin, DP ;
Green, DR ;
Salvesen, GS .
MOLECULAR CELL, 2003, 11 (02) :529-541
[3]  
CHENG SN, 2000, P INT WORKSH ANN COM, V1, P275
[4]   Caspase-activation pathways in apoptosis and immunity [J].
Creagh, EM ;
Conroy, H ;
Martin, SJ .
IMMUNOLOGICAL REVIEWS, 2003, 193 (01) :10-21
[5]  
FERNANDESALNEMRI T, 1995, CANCER RES, V55, P2737
[6]   Role of caspase 1 in neurologic disease [J].
Friedlander, RM .
ARCHIVES OF NEUROLOGY, 2000, 57 (09) :1273-1276
[7]   Expression of a dominant negative mutant of interleukin-1 beta converting enzyme in transgenic mice prevents neuronal cell death induced by trophic factor withdrawal and ischemic brain injury [J].
Friedlander, RM ;
Gagliardini, V ;
Hara, H ;
Fink, KB ;
Li, WW ;
MacDonald, G ;
Fishman, MC ;
Greenberg, AH ;
Moskowitz, MA ;
Yuan, JY .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (05) :933-940
[8]  
GRIFFIN WST, 1989, P NATL ACAD SCI USA, V86, P7611
[9]   Sequential and rapid activation of select caspases during apoptosis of normal intestinal epithelial cells [J].
Grossmann, J ;
Mohr, S ;
Lapetina, EG ;
Fiocchi, C ;
Levine, AD .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1998, 274 (06) :G1117-G1124
[10]   Active caspase-6 and caspase-6-cleaved Tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease [J].
Guo, HS ;
Albrecht, S ;
Bourdeau, M ;
Petzke, T ;
Bergeron, C ;
LeBlanc, AC .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 165 (02) :523-531