Mitochondria have emerged as the central components of both caspase-dependent and independent apoptosis signalling pathways through release of different apoptogenic proteins. We previously documented that parental and differentiated Friend's erythroleukemia cells were induced to apoptosis by oligomycin and H(2)O(2) exposure, showing that the energy impairment occurring in both cases as ...

Na(+)/H(+) exchanger (NHE-1) inhibition was demonstrated to induce the regression of cardiac hypertrophy (CH) in several experimental models and to inhibit mitochondrial death pathway in "in-vitro" experiments. Since recent reports show that NHE-1 inhibition delays the transition from CH to failure, and apoptosis plays a key role in this process, ...

The mitochondria are the major intracellular source of reactive oxygen species (ROS), which are generated during cellular respiration. The role of peroxiredoxin (Prx) III, a 2-Cys Prx family member, in the scavenging of mitochondrial H(2)O(2) has recently been emphasized. While eliminating H(2)O(2), Prx can become overoxidized and inactivated by modifying ...

Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human ...

Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken ...

Tumor necrosis factor alpha (TNF) is a cytokine that induces caspase-dependent (apoptotic) and caspase-independent (necrosis-like) cell death in different cells. We used the murine fibrosarcoma cell line model L929 and a stable L929 transfectant over-expressing a mutated dominant-negative form of BNIP3 lacking the C-terminal transmembrane (TM) domain (L929-DeltaTM-BNIP3) to test ...

One obstacle of cancer therapy is the development of cancer resistance to chemotherapy. The molecular mechanisms by which the resistance is developed remain to be fully understood. Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous antiapoptotic protein. Here, we report that ARC contributes to chemotherapy resistance by abolishing ...

Individual cells within a population undergo apoptosis at distinct, apparently random time points. By analyzing cellular mitotic history, we identified that sibling HeLa cell pairs, in contrast to random cell pairs, underwent apoptosis synchronously. This allowed us to use high-speed cellular imaging to investigate mitochondrial outer membrane permeabilization (MOMP), a ...

BACKGROUND: Vascular smooth-muscle cell proliferation plays an important role in atherosclerosis and restenosis. Rhein is an active component extracted from rhubarb. In this study, rhein was found to exert potent inhibitory effects against tumor necrosis factor (TNF)-alpha-induced human aortic smooth-muscle cells (HASMCs) proliferation. METHOD: These effects were associated with induced ...

We have evaluated the toxicity of four glyphosate (G)-based herbicides in Roundup formulations, from 10(5) times dilutions, on three different human cell types. This dilution level is far below agricultural recommendations and corresponds to low levels of residues in food or feed. The formulations have been compared to G alone ...

During therapeutic hyperbaric oxygenation lymphocytes are exposed to high partial pressures of oxygen. This study aimed to analyze the mechanism of apoptosis induction by hyperbaric oxygen. For intervals of 0.5-4 h Jurkat-T-cells were exposed to ambient air or oxygen atmospheres at 1-3 absolute atmospheres. Apoptosis was analyzed by phosphatidylserine externalization, ...

It is well known that TP53 may mediate apoptosis triggered by anticancer drugs. However, accumulating evidence indicates that TP53 may be inactivated by mutations and/or deletions in about 50% of human cancers and, as such, may lead to pronounced resistance to therapeutic agents. Thus, the development of new approaches to ...

The past decade has seen the emergence of a new mechanistic paradigm of cancer therapeutics. Not only have mitochondria taken centre stage as key cellular organelles mediating intrinsic pathways of cell death by apoptosis, but nonapoptotic pathways have also been shown to involve mitochondrial mechanisms. Both pathways of cell death ...

A major obstacle in cancer chemotherapy is the phenomenon of multidrug resistance (MDR), increased P-glycoprotein expression, and abnormal apoptotic processes that may contribute to MDR. Our previous studies demonstrated that JWA is a pro-apoptotic molecule and required for arsenic trioxide and all-trans-retinoic acid-induced cancer cell apoptosis. In this study, the ...

The critical role of mitochondria in programmed cell death leads to the design of mitochondriotropic agents as a strategy in regulating apoptosis. For anticancer therapy, stimulation of proapoptotic mitochondrial events in tumor cells and their suppression in surrounding normal cells represents a promising paradigm for new therapies. Different approaches targeting ...

Fifteen years of apoptosis research have led to the widely accepted idea that the major form of programmed cell death in mammals proceeds via the mitochondria, and that mitochondrial control of apoptosis is regulated by a specialized family of proteins known as the Bcl-2 family. Here we will consider some ...

Mitochondria play key roles in activating apoptosis in mammalian cells. Bcl-2 family members regulate the release of proteins from the space between the mitochondrial inner and outer membrane that, once in the cytosol, activate caspase proteases that dismantle cells and signal efficient phagocytosis of cell corpses. Here we review the ...

The present study examined the effects of KIOM-79 on streptozotocin (STZ)-induced mitochondrial oxidative stress in rat pancreatic beta-cells (RINm5F). KIOM-79 is a mixture of plant extracts from parched Puerariae radix, gingered Magnoliae cortex, Glycyrrhizae radix, and Euphorbiae radix. A marked increase in mitochondrial reactive oxygen species (ROS) was observed in ...

The present study evaluated the molecular mechanism of antidiabetic property of G. montanum leaf extract (GLEt) against alloxan-induced apoptotic cell death in rat insulinoma cells (RINm5F). The pre-treatment of GLEt (5 microg and 10 microg/ml) resulted in significant decrease in intracellular Ca(2+) concentration, nitric oxide (NO) production along with increase ...

Titanium dioxide (TiO(2)), a commercially important material, is used in a wide variety of products. Although TiO(2) is generally regarded as nontoxic, the cytotoxicity, pathogenicity, and carcinogenicity of TiO(2) nanoparticles have been recently recognized. The present study investigated TiO(2) nanoparticle-induced cell apoptosis and molecular mechanisms involved in this process in ...

There is an increasing evidence that uncoupling protein-2 (UCP2), a recently identified molecular sensor and suppressor of mitochondrial reactive oxygen species (ROS), plays an important role in -regulating apoptosis in different cell systems. A great technical difficulty that many groups have encountered is the reliable detection of endogenously or exogenously ...

There are many organelles within a cell, each with individual responsibilities required for life. Of these organelles, the mitochondria are the hemi of the cell, producing the energy necessary for cell function. Reactive oxygen species can cause mitochondrial dysfunction and contribute to many diseases often seen in emergency departments. When ...

Cancer chemoprevention employs agents that block, hinder, or reverse tumorigenesis to prevent malignancy. Several putative cancer chemopreventive agents promote apoptosis in transformed cells initiated in animal carcinogenesis models or identified in human subjects, and/or in tumor cells cultured in vitro. Consequently, apoptosis induction is increasingly valued as a biologically significant ...

Lithium (Li) is still useful in the treatment of bipolar disorder. Cellular mechanisms of Li action are not fully understood and include some cytoprotective properties. Data concerning Li effect on the apoptotic mechanisms in cells other than neurons are fragmentary and contradictory. We have investigated anti-apoptotic activity of Li in ...

BACKGROUND: The product of a novel cytokine-responsive gene discovered by differential display analysis in our earlier studies on HepG2 cells was identified as mimitin - a small mitochondrial protein. Since proinflammatory cytokines are known to affect components of the respiratory chain in mitochondria, and mimitin was reported as a possible ...

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. ...

BACKGROUND: The mitochondrial voltage-dependent anion channel (VDAC) is increasingly implicated in the control of apoptosis. We have studied the effects the mitochondrial DNA (mtDNA) tRNAIle mutation on VDAC expression, localization, and apoptosis. METHODS: Lymphoblastoid cell lines were derived from 3 symptomatic and 1 asymptomatic members of a family with hypertension ...

The innate immune response to viral infection involves the activation of multiple signaling steps that culminate in the production of type I interferons (IFNs). Mitochondrial antiviral signaling (MAVS), a mitochondrial outer membrane adaptor protein, plays an important role in this process. Here, we report that mitofusin 2 (Mfn2), a mediator ...

Capsaicin is widely used as a food additive and as an analgesic agent. Besides its well-known role in nociception, which is mediated by vanilloid receptor 1 specifically expressed in dorsal root ganglion neurons, capsaicin has also been considered as a potential anticancer agent, as it inhibits cell proliferation and induces ...

Adenine nucleotide translocase (ANT) is known as a core component of the mitochondrial permeability transition pore (MPTP) and a key player in cell death. However, its role in camptothecin (CPT)-induced apoptosis has not been examined. We showed that CPT-induced apoptosis in QGY7703 cells and down-regulated the expression of ANT3. Using ...

Benzothiazoles are multitarget agents with broad spectrum of biological activity. 2-Acetyl-3-(6-methoxybenzothiazo)-2-yl-amino-acrylonitrile (AMBAN) is a new synthetically prepared derivative, which in our previous study showed cytotoxic effects towards tumor cells. The aim of the present study was to examine the antiproliferative and apoptosis inducing activities of AMBAN towards human leukemia HL60 ...

Mitochondria are dynamic organelles that play key roles in metabolism, energy production, and apoptosis. Coordination of these processes is essential to maintain normal cellular functions. Here we characterized hNOA1, the human homologue of AtNOA1 (Arabidopsis thaliana nitric oxide-associated protein 1), a large mitochondrial GTPase. By immunofluorescence, immunoelectron microscopy, and mitochondrial ...

Glucagon like peptide-1 (Glp-1) exhibits beneficial effects on beta cell mass by both enhancing proliferation and inhibiting apoptosis. The precise mechanism of the anti-apoptotic effect of Glp-1 and Glp-1 mimetics like exendin-4 has remained elusive. Here, we studied cytokine-induced apoptosis in the pancreatic beta cell line INS-1 and performed a ...

Timosaponin A-III (TAIII), a saponin isolated from the rhizome of Anemarrhena asphodeloides, exhibits potent cytotoxicity and has the potential to be developed as an anticancer agent. Here, we provide evidence that TAIII induces autophagy in HeLa cells followed by apoptotic cell death. TAIII-induced autophagy was morphologically characterized by the formation ...

Reactive oxygen species (ROS) have been implicated in oxysterol-induced apoptosis. However, the mechanism of ROS production induced by oxysterols within cells is not clear. Considering that mitochondria is the main source of intracellular ROS, and play a key role in oxysterol-induced apoptosis, we investigated the effect of oxysterol cholestane-3beta,5alpha,6beta-triol (Triol) ...

In view of the controversial role of catalytic activity on the cytotoxicity of phospholipase A(2) (PLA(2)), the present study is conducted to explore whether PLA(2) induces apoptotic process of human leukemia U937 cells through catalytic activity-independent pathway. Modification of His-48 (according to the sequence alignment with porcine pancreatic PLA(2)) with ...

We have investigated the role of mitochondria on the development of indomethacin (a non-steroidal anti-inflammatory drug)-induced gastric mucosal apoptosis and associated gastropathy in rat. Transmission electron microscopic studies indicate that indomethacin damages mitochondrial ultrastructure and causes mitochondrial dysfunction as evident from decreased stage-3 respiration, dehydrogenase activity, and transmembrane potential (DeltaPsi(m)). ...

Mitochondrial dysfunction is implicated in many forms of cell death, particularly in the central nervous system. The mitochondria are required at the same time to generate adenosine 5'-triphosphate (ATP) for the cell, sequester excess cytoplasmic Ca(2+), and both produce and detoxify superoxide free radicals. The electron transport chain and proton ...

To explore how the intrinsic apoptosis pathway is controlled in the spontaneous fog (forebrain overgrowth) mutant mice with an Apaf1 splicing deficiency, we examined spleen and bone marrow cells from Apaf1(+/+) (+/+) and Apaf1(fog/fog) (fog/fog) mice for initiator caspase-9 activation by cellular stresses. When the mitochondrial inner membrane potential (Deltapsim) ...

PURPOSE: Interleukin-(IL)1beta expression is increased in the retina during a variety of diseases involving the death of retinal neurons and contributes to neurodegenerative processes through an unknown mechanism. This study was conducted to examine the effects of IL-1beta on the metabolism and viability of RGC-5 and R28 retinal neuronal cells. ...

The purpose of this article was to study the effect of hyaluronic acid (HA) on chondrocyte apoptosis in a rat osteoarthritis in vitro model (exposure to IL-1beta) and explore its mechanism. A rat in vitro model of osteoarthritis (OA) was established using 10 ng/mL IL-1beta as a modulating and chondrocyte ...

Glycyrrhizic acid (GA) is the main bioactive ingredient of licorice (Glycyrrhiza glabra). The object of this study was to evaluate the protective effects of GA on tert-butyl hydroperoxide (t-BHP) induced oxidative injury leading to apoptosis in cultured primary rat hepatocytes. Throughout the study silymarin was used as positive control. Molecular ...

Mutations in Cu, Zn-superoxide dismutase 1 (SOD1) are associated with degeneration of motor neurons in the disease, familial amyotrophic lateral sclerosis. Intracellular protein inclusions containing mutant SOD1 (mSOD1) are associated with disease but it is unclear whether they are neuroprotective or cytotoxic. We report here that the formation of mSOD1 ...

Mitochondrial (mt)DNA mutations contribute to various disease states characterized by low ATP production. In contrast, thyroid hormone [3,3',5-triiodothyronine (T(3))] induces mitochondrial biogenesis and enhances ATP generation within cells. To evaluate the role of T(3)-mediated mitochondrial biogenesis in patients with mtDNA mutations, three fibroblast cell lines with mtDNA mutations were evaluated, ...

To elucidate the significance of mitochondrial localization of Cu/Zn-SOD (SOD1), we studied the relationship between the release of mitochondrial SOD1 and apoptosis. Kinetic analysis using HL-60 cells showed that both mitochondria-dependent and mitochondria-independent pro-apoptotic drugs, such as staurosporine and actinomycin D, increased the generation of reactive oxygen species (ROS) and ...

Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human disorder Barth syndrome. Using Barth syndrome patient-derived ...

Eosinophils (Eo) are typically associated with immune response to helminth. Previously, we demonstrated that excretory-secretory products (ESP) from Fasciola hepatica induce eosinophil apoptosis by a caspase-dependent mechanism. In this study, we observed that ESP caused mitochondrial-membrane depolarization of eosinophils leading to the release of cytochrome c. Also, ESP induced an ...

Hyperosmotic stress represents a major threat to cellular integrity and may lead to cell death via apoptosis. Accordingly, each cell reacts to hyperosmolarity with a set of functional and structural compensatory responses. Recently it has been shown that the mitochondria remodel during hyperosmotic stress. Although changes in mitochondrial dynamics could ...

While mitochondria are traditionally associated with energy production, recent studies identified its function in controlling the onset of apoptosis. Mitochondrial apoptotic control results from sequestering pro-apoptotic proteins, which are secreted following cellular stress. HtrA2/OMI is secreted from mitochondria to the cytosol following apoptotic induction, binds and degrades the inhibitor of ...

Activation of the mitochondrial apoptosis pathway by oxidative stress has been implicated in hepatocyte apoptosis during malaria. Because mitochondria are the source and target of reactive oxygen species (ROS), we have investigated whether hepatocyte apoptosis is linked to mitochondrial pathology and mitochondrial ROS generation during malaria. Malarial infection induces mitochondrial ...