scholarly journals Interleukin-1β converting enzyme: A novel cysteine protease required for IL-1β production and implicated in programmed cell death

1995 ◽  
Vol 4 (1) ◽  
pp. 3-12 ◽  
Author(s):  
Nancy A. Thornberry ◽  
Susan M. Molineaux
1997 ◽  
Vol 185 (4) ◽  
pp. 601-608 ◽  
Author(s):  
Stefanie Dimmeler ◽  
Judith Haendeler ◽  
Michael Nehls ◽  
Andreas M. Zeiher

Physiological levels of shear stress alter the genetic programm of cultured endothelial cells and are associated with reduced cellular turnover rates and formation of atherosclerotic lesions in vivo. To test the hypothesis that shear stress (15 dynes/cm2) interferes with programmed cell death, apoptosis was induced in human umbilical venous cells (HUVEC) by tumor necrosis factor-α (TNF-α). Apoptosis was quantified by ELISA specific for histone-associated DNA-fragments and confirmed by demonstrating the specific pattern of internucleosomal DNA-fragmentation. TNF-α (300 U/ml) mediated increase of DNA-fragmentation was completely abrogated by shear stress (446 ± 121% versus 57 ± 11%, P <0.05). This anti-apoptotic activity of shear stress decreased after pharmacological inhibition of endogenous nitric oxide (NO)-synthase by NG-monomethyl-l-arginine and was completely reproduced by exogenous NO-donors. The activation of interleukin-1β–converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like cysteine proteases was required to mediate TNF-α–induced apoptosis of HUVEC. Endothelial-derived nitric oxide (NO) as well as exogenous NO donors inhibited TNF-α–induced cysteine protease activation. Inhibition of CPP-32 enzyme activity was due to specific S-nitrosylation of Cys 163, a functionally essential amino acid conserved among ICE/CPP-32–like proteases. Thus, we propose that shear stress-mediated NO formation interferes with cell death signal transduction and may contribute to endothelial cell integrity by inhibition of apoptosis.


1997 ◽  
Vol 17 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Minoru Asahi ◽  
Minoru Hoshimaru ◽  
Yoshihiko Uemura ◽  
Tomoo Tokime ◽  
Masahiro Kojima ◽  
...  

Recent investigations have been suggesting that some neuronal subpopulations may die via programmed cell death after focal ischemic injury. To clarify the possible roles of the genes involved in the cell-death program, this study examined the expression of three members of the interleukin-1β converting enzyme ( Ice) gene family ( Ice, Nedd2, and Yama/CPP32) and two members of the bcl-2 gene family ( bcl-2 and bcl-x) in the rat brain after permanent occlusion of the middle cerebral artery. Northern blot analysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of Ice remained constant. The expression of bcl-2 and bcl-x remained constant after the ischemic insult. Taking into account the key role of the Ice gene family in the execution of programmed cell death, the induction of Ice gene family might play a causative role in apoptotic cell death.


2014 ◽  
Vol 26 (7) ◽  
pp. 2939-2961 ◽  
Author(s):  
Dandan Zhang ◽  
Di Liu ◽  
Xiaomeng Lv ◽  
Ying Wang ◽  
Zhili Xun ◽  
...  

Cell ◽  
1994 ◽  
Vol 78 (2) ◽  
pp. 343-352 ◽  
Author(s):  
N.P.C. Walker ◽  
R.V. Talanian ◽  
K.D. Brady ◽  
L.C. Dang ◽  
N.J. Bump ◽  
...  

1999 ◽  
Vol 19 (6) ◽  
pp. 634-642 ◽  
Author(s):  
Yuiko Morita-Fujimura ◽  
Miki Fujimura ◽  
Makoto Kawase ◽  
Kensuke Murakami ◽  
Gyung Whan Kim ◽  
...  

The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with z-VAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the z-VAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 ± 1.80 mm3, z-VAD.FMK-treated animals; 7.46 ± 3.53 mm3, vehicle-treated animals; mean ± SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1β converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after cold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family proteases appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.


2005 ◽  
Vol 102 (40) ◽  
pp. 14463-14468 ◽  
Author(s):  
P. V. Bozhkov ◽  
M. F. Suarez ◽  
L. H. Filonova ◽  
G. Daniel ◽  
A. A. Zamyatnin ◽  
...  

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