Although apoptosis occurs during myogenesis, its mechanism of initiation remains unknown. In a culture model, we demonstrate activation of caspase-12, the initiator of the endoplasmic reticulum (ER) stress-specific caspase cascade, during apoptosis associated with myoblast differentiation. Induction of ER stress-responsive proteins (BiP and CHOP) was also observed in both apoptotic and differen...

Many molecules are inducibly localized in lipid rafts, and their alteration inhibits early activation events, supporting a critical role for these domains in signaling. Using confocal microscopy and cellular fractionation, we have shown that the pool of Bad, attached to lipid rafts in proliferating cells, is released when cells undergo apoptosis. Kinetic studies indicate that rafts alteration i...

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) binds to death receptors 4/5 and selectively induces caspase-dependent apoptosis. The RNA interference screening approach has led to the discovery and characterization of several TRAIL pathway components in human cells. Here, libraries of synthetic small interfering RNA (siRNA) and microRNAs (miRNA) were used to probe the TRAIL pat...

Increasing evidence suggests a role for apoptosis in the maintenance of the alveolar epithelium under normal and pathological conditions. However, the signaling pathways modulating alveolar type II (AT II) cell apoptosis remain poorly defined. Here we investigated the role of lysosomes as modulators of oxidant-mediated AT II cell apoptosis using an in vitro model of H(2)O(2)-stress. H(2)O(2) st...

Caspases are central components in the apoptosis signaling cascade. The family of cysteine proteases transduces and enhances the apoptosis signal, and activation of effector caspases results in controlled cellular degradation. Although initially the presence of caspases in spermatozoa was controversially discussed in recent years, many studies demonstrated their activation in male germ cells. A...

In this study antiproliferation, cell cycle arrest and apoptosis induced by daphnoretin in human osteosarcoma (HOS) cells were investigated. Antiproliferative activity was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The IC(50) value of daphnoretin was 3.89 μM after 72 h treatment. Induction of apoptosis was evidenced by apoptotic body appearance a...

The binding of Fas ligand to Fas recruits caspase 8 to Fas via an adaptor, FADD/MORT1, and activates a caspase cascade leading to apoptosis. Here, we describe a human Jurkat-derived cell line (JB-6) that is deficient in caspase 8. This cell line was resistant to the apoptosis triggered by Fas engagement. However, the multimerization of Fas-associated protein with death domain, through the use o...

Apoptosis is initiated via the mitochondrial or the death receptor pathway. Central to the mitochondrial pathway is the release of cytochrome c from the mitochondria, leading to activation of the caspase cascade and execution of apoptosis.1 The mitochondrial pathway is regulated by the BCL-2 family of proteins, i.e. proapoptotic BAX and BAK as well as antiapoptotic BCL-2 and BCL-xL. The death r...

OBJECTIVES Septic shock and sequential multiple organ failure remain the cause of death in septic patients. Vascular endothelial cell apoptosis may play a role in the pathogenesis of the septic syndrome. Caspase-8 is presumed to be the apex of the death receptor-mediated apoptosis pathway, whereas caspase-3 belongs to the "effector" protease in the apoptosis cascade. Synthetic small interfering...