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Whilst the role of ceramide, a second messenger of the sphingolipid family, in the initiation of receptor-mediated apoptosis is controversial, a growing body of evidence is emerging for a role of ceramide in the amplification of apoptosis via mitochondrial perturbations that culminate in the activation of execution caspases. Treatment of Jurkat T cells with the cell-permeable analog, C2-ceramide,...
Bid is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for death receptor-mediated apoptosis in many cell systems. Bid action has been proposed to involve the mitochondrial re-location of its truncated form, tBid, to facilitate the release of apoptogenic proteins like cytochrome c. However, the precise mechanism of (t)Bid action is unknown. To advance our knowledge, this review...
Apoptotic response of keratinocytes to UVB irradiation has physiological significance on photocarcinogenesis. Here, we show that the sustained release of Smac/DIABLO from mitochondria is an important event for the onset of apoptosis in keratinocytes exposed to UVB irradiation. In human keratinocyte HaCaT cells, UVB irradiation at 500 J/m2, but not at 150 J/m2, induces apoptosis. Significant activations...
The apoptosis effector Bid regulates cell death at the level of mitochondrial cytochrome c efflux. Bid consists of 8 α-helices (designated H1 through H8, respectively) and is a soluble cytosolic protein in its native state. Proteolysis of the N-terminus (encompassing H1 and H2) of Bid yields activated “tBid” (truncated Bid), which translocates to the mitochondria and induces the efflux of cytochrome...
Recent observations show a positive correlation between the expression of cyclooxygenase (COX), especially COX-2), and cancer development. Here we tested the hypothesis that expression of COX-2 could influence apoptosis in lung cancer cell lines. To address this question, we determined the effects of camptothecin-induced apoptosis on three lung cancer cell lines which over express COX-1 (CORL23),...
HL-60 cell differentiation into neutrophil like cells is associated with their induction of apoptosis. We investigated the cellular events that occur pre and post mitochondrial permeability transition to determine the role of the mitochondria in the induction of differentiation induced apoptosis. Pro-apoptotic Bax was translocated to and cleaved at the mitochondrial membrane in addition to t-Bid activation...
A non-traumatic electroporation procedure was developed to load exogenous cytochrome c into the cytoplasm and to study the apoptotic effect of cytochrome c, its K72-substitued mutants and “yeast → horse” hybrid cytochrome c in living WEHI-3 cells. The minimum apoptosis-activating intracellular concentration of horse heart cytochrome c was estimated to be 2.7 ± 0.5 μM (47 ± 9 fg/cell). The equieffective...
Here we show a detailed analysis of cellular and molecular events during in vivo apoptotic cell death in the INZs (interdigital necrotic zones) of the embryonic limb. As the apoptotic mechanisms proceed, the transcriptionally active chromatin and nuclear traffic of RNAs are disrupted, cytoskeletal components are disorganized and the adhesive properties of cells are compromised as Paxillin, a clue...
Telomerase activation represents an early step in carcinogenesis. Increased telomerase activity in cervical cancer suggests a potential target for the development of novel therapeutic drugs. The aim of this study is to investigate the impact of telomerase activity on the biological features of HeLa cells and the possible mechanisms of enhanced apoptosis rate induced by sodium butyrate after telomerase...
Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived...
Cytochrome c (Cyt c) has been implicated as a serum marker for aberrant apoptosis and, thus, has considerable clinical potential. Using a sandwich enzyme-linked immunosorbent assay (ELISA) we found that the sensitivity of Cyt c detection is reduced in the presence of serum. The inhibitory factor responsible was purified from both fetal bovine serum and human serum employing standard chromatography...
Combined treatment modalities using tumor necrosis factor related apoptosis-inducing ligand L (TRAIL) and cytotoxic drugs revealed highly additive effects in some tumor cell lines. Little is known about the efficacy and underlying mechanistic effects of the modalities in chemoresistant tumor cells. The purpose of this study is to investigate the possible role of JNK in the synergistic effect in Doxorubicin...
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of a photosensitizer, light and oxygen. PDT with the endogenous photosensitizer, protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) or its derivatives is a modification of this treatment modality with successful application in dermatology. However, the mechanism of cell destruction by ALA-PDT has not been elucidated...
Expression of HSV-1 genes leads to the induction of apoptosis in human epithelial HEp-2 cells but the subsequent synthesis of infected cell protein prevents the process from killing the cells. Thus, viruses unable to produce appropriate prevention factors are apoptotic. We now report that the addition of either a pancaspase inhibitor or caspase-9-specific inhibitor prevented cells infected with an...
Peptidylarginine deiminase IV (PADI4) posttranslationally converts peptidylarginine to citrulline. It plays an essential role in immune cell differentiation and apoptosis. A haplotype of single-nucleotide polymorphisms (SNPs) in PADI4 is functionally relevant as a rheumatoid arthritis (RA) gene. It could increase enzyme activity leading to raised levels of citrullinated protein and stimulating autoantibody...
The induction of apoptosis during coxsackievirus B3 (CVB3) infection is well documented. In order to study whether the inhibition of apoptosis has an impact on CVB3 replication, the pan-caspase inhibitor Z-VAD-FMK was used. The decreased CVB3 replication is based on reduced accumulation of both viral RNA and viral proteins. These effects are due to an inhibitory influence of Z-VAD-FMK on the proteolytic...
Toxoplasma gondii is an intracellular parasite able to both promote and inhibit apoptosis. T. gondii renders infected cells resistant to programmed cell death induced by multiple apoptotic triggers. On the other hand, increased apoptosis of immune cells after in vivo infection with T. gondii may suppress the immune response to the parasite. Glycosylphosphatidylinositol (GPI)-anchored proteins dominate...
Nervous necrosis virus (NNV)-induced, host cell apoptosis mediates secondary necrosis by an ill-understood process. In this study, redspotted grouper nervous necrosis virus (RGNNV) is shown to induce mitochondria-mediated necrotic cell death in GL-av cells (fish cells) via cytochrome c release, and anti-apoptotic proteins are shown to protect these cells from death. Western blots revealed that cytochrome...
Fas-induced apoptosis is initiated through the recruitment of FADD and procaspase 8 to form the death-inducing signaling complex (DISC). In some cells (type I cells) the initiator caspase 8 directly activates effector caspases such as procaspase 3, whereas in others (type II cells) the death signal is amplified through mitochondria. In epithelial cells, Fas-induced hierarchic caspase activation is...
Pancreatic cancer is one of the most common invasive malignancies and the fourth leading cause of cancer related mortality in U.S., thus developing new strategies to control pancreatic cancer is an important mission. We investigated the mechanism of capsaicin, the major pungent ingredient of red-chili pepper, in inducing apoptosis in pancreatic cancer cells. Treatment of AsPC-1 and BxPC-3 cells with...
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