Glioblastoma (GBM) is an astrocytic brain tumor characterized by an aggressive clinical course and intense resistance to all therapeutic modalities. Here, we report the identification and functional characterization of Bcl2L12 (Bcl2-like-12) that is robustly expressed in nearly all human primary GBMs examined. Enforced Bcl2L12 expression confers marked apoptosis resistance in primary cortical a...

The regulation of neutrophil recruitment, activation, and disposal is pivotal for circumscribed inflammation. SHP1(Y208N/Y208N) mutant mice develop severe cutaneous inflammatory disease that is IL-1R dependent. Genetic reduction in neutrophil numbers and neutrophilic responses to infection is sufficient to prevent the spontaneous initiation of this disease. Neutrophils from SHP1(Y208N/Y208N) mi...

Lethal hepatitis can be induced by an agonistic anti-Fas Ab in normal mice or by TNF in mice sensitized to d -(+)-galactosamine or actinomycin D. In all three models, we found that apoptosis of hepatocytes is an early and necessary step to cause lethality. In the three models, we observed activation of the major executioner caspases-3 and -7. Two acute-phase proteins, alpha1-acid glycoprotein a...

The pathogenesis of equine grass sickness (EGS) has not fully understood. A better understanding of the exact pathogenesis of diseases can help to make an accurate diagnosis. Previous studies reported some pathological damage of neuronal cells in EGS patients. In this study, primarily cytotoxicity of serum from three clinically EGS-diagnosed horses on PC12 Tet-off (PTO) cells was assessed. Subs...

Inhibitor of apoptosis (IAP) gene products play an evolutionarily conserved role in regulating programmed cell death in diverse species ranging from insects to humans. Human XIAP, cIAP1 and cIAP2 are direct inhibitors of at least two members of the caspase family of cell death proteases: caspase-3 and caspase-7. Here we compared the mechanism by which IAPs interfere with activation of caspase-3...

BACKGROUND Human periodontal ligament (PDL) cells underwent apoptosis after mechanical stretch loading. However, the exact signalling pathway remains unknown. This study aimed to elucidate how the apoptotic caspases functioned in the cyclic stretch-induced apoptosis in human PDL cells. MATERIALS AND METHODS In the present study, 20% cyclic stretch was selected to load the cells for 6 or 24 h....

The inhibitor of apoptosis proteins (IAPs) represent the only endogenous caspase inhibitors and are characterized by the presence of baculoviral IAP repeats (BIRs). Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker). The structure surprisingly reveals that the linker is the only contacting element for the caspase, while the BIR...

Statins are lipid-lowering drugs that may help limit cancer occurrence in humans. They drive blockage of the mevalonate pathway, trigger cancer cell apoptosis in vitro and reduce tumour incidence in animals. We have shown in the present study that statins induced apoptosis in HGT-1 human gastric cancer cells, and this was prevented by intermediates of the cholesterol synthetic pathway. In addit...

Activation of caspase-mediated apoptosis is reported to be a hallmark of both granzyme B- and Fas-mediated pathways of killing by CTLs; however, the kinetics of caspase activation remain undefined owing to an inability to monitor target cell-specific apoptosis in real time. We have overcome this limitation by developing a novel biosensor assay that detects continuous, protease-specific activity...

We reported recently that roscovitine arrested human MCF-7 cancer cells at G2-M phase of the cell cycle and concomitantly induced apoptosis. After roscovitine treatment, the level of wild-type p53 protein strongly increased and p53 was accumulated in the nucleus. Here, we raised the question of which pathway would be involved in roscovitine-induced apoptosis in MCF-7 cells, which are known to b...