2-Methoxyestradiol (2ME), an endogenous metabolite of 17beta-estradiol, has been reported to play an active role in the induction of apoptosis in both proliferating endothelial and cancer cells. Since it has been indicated that an increased ratio of pro-apoptotic Bax protein to anti-apoptotic Bcl-2 protein expression can be associated with apoptosis, ...

Oxysterols, and particularly 7-ketocholesterol, appear to be strongly involved in the physiopathology of atherosclerosis. These molecules are suspected to be cytotoxic to the cells of the vascular wall and monocytes/macrophages, particularly by inducing apoptosis. Previous studies have demonstrated that 7-ketocholesterol-induced apoptosis is triggered by a sustained increase of cytosolic-free Ca2+, ...

Proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-X(L) and Bcl-2, are overexpressed in many cancers and contribute to tumour initiation, progression and resistance to therapy. Bcl-X(L) expression correlates with chemo-resistance of tumour cell lines, and reductions in Bcl-2 ...

Postmenopausal women with estrogen receptor positive (ER(+)) breast cancer frequently respond paradoxically to estrogen administration with tumor regression. Using both LTED and E8CASS cells derived from MCF-7 breast cancer cells by long-term estrogen-deprivation, we previously reported that 17beta -estradiol (estradiol) is a powerful, pro-apoptotic hormone which kills the cancer cells ...

The mitochondrial cell death pathway is known for its role in signaling apoptosis. Here, we describe a novel function for the mitochondrial cell death pathway in signaling initiation of differentiation in the developing lens. Most remarkably, we induced lens cell differentiation by short-term exposure of lens epithelial cells to the ...

Chronic obstructive pulmonary disease (COPD) is an inflammatory airway disease, usually associated with cigarette smoking. Stimulated peripheral blood T cells from patients with COPD have an increased propensity to undergo apoptosis. The mitochondrial apoptotic pathway is regulated by pro-apoptotic proteins (including p53 and Bax) as well as anti-apoptotic proteins (e.g. ...

Hyperoxic acute lung injury (HALI) is characterized by a cell death response with features of apoptosis and necrosis that is inhibited by IL-11 and other interventions. We hypothesized that Bfl-1/A1, an antiapoptotic Bcl-2 protein, is a critical regulator of HALI and a mediator of IL-11-induced cytoprotection. To test this, we ...

Proteins of the Bcl-2 family are key regulators of apoptosis. Bax can be regarded as pro-apoptotic, whereas Bcl-2 is perceived as anti-apoptotic. It has been proposed that an increased ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2 can be associated with apoptosis. Since prostaglandin A2 (PGA2) and 2-methoxyestradiol (2-ME) play an ...

Chronic lymphocytic leukaemia (CLL) is the most common B-cell malignancy in the Western world and exists as subtypes with very different clinical courses. CLL is generally described as a disease of failed apoptosis. Apoptosis resistance may stem from a combination of microenvironmental survival signals as well as from intrinsic alterations ...

The pregnane X receptor (PXR) plays a major role in the protection of the body by regulating the genes involved in the metabolism and elimination of potentially toxic xeno- and endobiotics. We previously described that PXR activator dexamethasone protects hepatocytes from spontaneous apoptosis. We hypothesise a PXR-dependent co-regulation process between ...

A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level ...

Overexpression of anti-apoptotic Bcl-2 family members and deregulation of the pathways that regulate pro-apoptotic family members have been observed in non-small cell lung cancers (NSCLC). Previous reports have identified both Bcl-2 and Bcl-x(L) proteins as survival factors in lung cancer cells since reductions in these proteins can induce apoptosis and ...

BACKGROUND: The apoptosis action induced by hydroxyurea or etoposide in interleukin 3-dependent lymphoma cells (DA-1) was studied. MATERIALS AND METHODS: The conditions to study apoptosis of these cells were 17 hours of cell treatment with concentrations of 1.25 mM hydroxyurea or 100 microM etoposide using flow cytometry, fluorometry and immunoblots ...

Immunosuppressive drugs are routinely used to provide tolerance after whole pancreas and islet cell transplantations. While they are essential in inhibiting graft rejection, little is known about their effect on islet function and beta-cell viability. In this study, we report that tacrolimus, sirolimus, and mycophenolic acid, when added to cultures ...

BACKGROUND: Paracetamol overdose causes acute renal failure and chronic exposure to paracetamol has been linked to chronic renal failure. Recently, apoptosis induction has been identified as a possible mechanism of paracetamol nephrotoxicity. METHODS: Murine proximal tubular epithelial MCT cells were cultured in the presence of paracetamol. The effects of Bcl-xL ...

The primary cause of treatment failures in acute myeloid leukemia (AML) is the emergence of both resistant disease and early relapse. Among the most frequent agents of these phenomena are defects in the mitochondrial-mediated apoptotic pathway. This pathway is regulated by bcl-2 family of anti-apoptotic (bcl-2, bcl-xl, mcl-1) and pro-apoptotic ...

Mcl-1 is a Bcl-2 family protein which can act as an apical molecule in apoptosis control, promoting cell survival by interfering at an early stage in a cascade of events leading to release of cytochrome c from mitochondria. Mcl-1 has a short half life and is a highly regulated protein, ...

Mast cells play critical roles in the regulation of acute and chronic inflammations. Apoptosis is one of the mechanisms that limit and resolve inflammatory responses. Mast cell survival can be controlled by growth factors and activation of the IgE-receptor FcvarepsilonRI. Members of the Bcl-2 protein family are critical regulators of ...

The Bcl-2 family of apoptotic-regulating proteins plays important roles during both neural development and maintenance of tissue homeostasis. The major antiapoptotic family members, Bcl-x(L) and Bcl-2, and the major proapoptotic proteins, Bax and Bak, show distinct temporal and spatial patterns of expression in the developing brain. Targeted deletions of Bcl-x(L) ...

In a previous study, we showed that G3139, an antisense phosphorothioate oligonucleotide that down-regulates the expression of Bcl-2 protein, did not cause chemosensitization of 518A2 melanoma cells. In this work, we show that G3139, and the 2-base mismatch, G4126, can initiate apoptosis in this and other melanoma cell lines as ...

Cell death by apoptosis is important in immune cell homeostasis and in the defense against infectious microorganisms. The physiological event of uptake and intracellular destruction of bacteria is a powerful apoptotic stimulus to macrophages and neutrophil granulocytes. In this study, we provide a molecular analysis of phagocytosis-induced apoptosis. Apoptosis was ...

Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin, is present in high concentrations in dairy products and cereals. Studies have indicated that ZEA could strongly provoke proliferation in estrogen-dependent breast cancer MCF-7 cells following estrogen ablation. The current study confirmed the previous studies that within the range of concentrations of 2-96nM, like ...

The presence of a complete (BH1-3) proapoptotic molecule is necessary for the induction of the intrinsic apoptotic cascade in mammalian cells. It is unclear, however, what distinct roles the members of the large family of BH3-only proapoptotic molecules play in apoptosis. Although biochemical analysis of these molecules can characterize binding ...

Phosphatidylinositol 3-kinase (PI3K) and its effector protein kinase B (PKB/c-akt) have been implicated as critical mediators of cytokine-induced survival signals. In this study, we have utilized an IL-5 dependent hematopoietic cell line (TF-1) to investigate the signaling events involved in cytokine-dependent erythroblast survival. We demonstrate that IL-5 rescues TF-1 cells ...

It has been shown that Bcl-2 family members have an integral role in the maintenance of T-cell homeostasis. However, the mechanism by which these gene products are regulated is still not entirely known. This is true not only for the antiapoptotic protein Bcl-2 but for the pro-apoptotic protein Bim. Here ...

The Bcl-2 family of apoptotic regulators comprises both pro- and anti-apoptotic proteins. Pro-apoptotic BH3-only members of the Bcl-2 family are subject to stringent control in normal proliferating cells, but can be activated by a variety of mechanisms in response to diverse apoptotic signals. To facilitate the simultaneous identification of BH3-only ...

Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family, including Bcl-2 and Bcl-X(L), contributes to malignant transformation and subsequent resistance to traditional chemotherapeutics. Thus, these proteins represent attractive targets for novel anticancer agents. The small molecule, gossypol, was initially investigated as a contraceptive agent, but subsequently has been shown ...

BACKGROUND: Chronic lymphocytic leukemia (CLL) is characterized by accumulation of clonal, malignant CD5(+), CD23(+) B cells. In vivo, these cells have an antiapoptotic phenotype (high levels of Bcl-2 and low levels of proapoptotic Bcl-2 family proteins, such as Bax). Abnormal B cells accumulate due to altered apoptosis regulation rather than ...

Apoptosis or programmed cell death plays an important role in a wide variety of physiological processes. Apoptosis is regulated by proteins of the Bcl-2 family consisting of both anti-apoptotic and pro-apoptotic factors. The direct involvement of the Bcl-2 protein family in the process of mast cell apoptosis has not been ...

BACKGROUND: Apoptosis is a common and essential aspect of development. It is particularly prevalent in the central nervous system and during remodelling processes such as formation of the digits and in amphibian metamorphosis. Apoptosis, which is dependent upon a balance between pro- and anti-apoptotic factors, also enables the embryo to ...

In this study, we show that Bcl-2, one of the most important antiapoptotic agents, is expressed in a phase-dependent manner in the human adherent monocytes after vaccinia virus infection, reflecting the viral infection stages. Early viral infection induced Bcl-2 expression in a level higher than in control cells. At 14 ...

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-beta1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen ...

The zebrafish is an attractive vertebrate model for genetic studies of development, apoptosis, and cancer. Here we describe a transgenic zebrafish line in which T- and B-lymphoid cells express a fusion transgene that encodes the zebrafish bcl-2 protein fused to the enhanced green fluorescence protein (EGFP). Targeting EGFP-bcl-2 to the ...

Increased levels of Mcl-1 (myeloid cell factor-1) have been reported in several cancers, suggesting an important role played by Mcl-1 in cancer cell survival. Mcl-1 is an anti-apoptotic protein shown to delay or block apoptosis. In this work, using semiquantitative immunofluorescence, real-time PCR, and RNase protection assay, an increase in ...

The expression of the tumour suppressor protein fragile histidine triad (Fhit) is often impaired in many human cancers and its restoration in Fhit-negative cancer cell lines suppresses tumorigenicity and induces apoptosis. Although the proapoptotic function of Fhit is well documented, little is known about its precise mechanism of action and ...

Cancer cells generally maintain their survival by suppressing apoptosis. Mitochondrial mechanisms are involved in most forms of apoptosis (referred to as mitochondrial apoptosis), and the Bcl-2 family controls apoptosis at the mitochondrion via a balance of the effects of pro- and antiapoptotic members. Antiapoptotic molecules such as Bcl-2 and Bcl-x(L) ...

Enhanced expression of the apoptosis-preventing protein bcl-xL and the cell cycle-regulating protein p21 was observed in bone marrow infiltrates of systemic mastocytosis. Expression of bcl-2, Ki67, and p53 as well as ISEL apoptosis staining were comparable in patients with mastocytosis and in controls. An altered rate of apoptosis and cell ...

The Bcl-2 family of proteins has recently been implicated as a possible player in the complex cascade of neural cell death due to traumatic brain injuries. However, it is unclear if the Bcl-2 pathways are activated in mechanically injured neurons. Here we report the effects of BclX(L) and Bax over-expression ...

The most common form of human congenital muscular dystrophy (CMD) is caused by mutations in the laminin-alpha2 gene. Loss of laminin-alpha2 function in this autosomal recessive type 1A form of CMD results in neuromuscular dysfunction and, often, early death. Laminin-alpha2-deficient skeletal muscles in both humans and mice show signs of ...

Polychlorinated biphenyls (PCBs) are a group of persistent and widely dispersed environmental pollutants, some of which may be neurotoxic. In the present study, we have investigated the effect of PCB commercial mixtures (Aroclors) on neuronal cell cultures by assessing cell viability and apoptotic cell death. We have combined morphological and ...

Sinomenine (SN), an immunnosuppressive compound derived from the Chinese medicinal plant Sinomenium acutum, has been used to treat autoimmune diseases effectively. Previous studies show SN can inhibit lymphocytes proliferation and macrophage production of pro-inflammatory factors. However, little is known about the mechanisms by which SN inhibits macrophage functions. In this ...

Zinc is involved in many physiological processes and plays a critical role in functional and structural cells. Zinc at concentrations ranging from 100 to 150 micromol L(-1) has been shown to induce morphological transformation of Syrian hamster embryo (SHE) cells. At these concentrations, zinc inhibited apoptosis in SHE cells. The ...

The anti-estrogen 4-hydroxytamoxifen (TAM) and vitamin A-related compounds, the retinoids, in combination act synergistically to inhibit growth of breast cancer cells in vitro and in vivo. To clarify the mechanism of this synergism, the effect of TAM and all trans-retinoic acid (AT) on proliferation of MCF-7 breast cancer cells was ...

Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-x(L), are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role ...

Basal cell adhesion molecule (B-CAM) is strongly upregulated in epithelial skin cancer cells in vivo and in vitro. We have tested here whether B-CAM is (1) inversely associated with or (2) functionally involved in apoptosis. Towards this end, B-CAM expression was assessed in HaCaT transfectants overexpressing murine Bcl-2 and untransfected ...

Multiple myeloma is a fatal B cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 ...

In utero exposure to exogenous anti-androgenic compounds induces a wide range of abnormalities of the reproductive system, including hypospermatogenesis, cryptorchidism and hypospadias. By using rats exposed in utero to the anti-androgenic compound flutamide (0.4, 2 or 10 mg/kg per day), it has been shown that hypospermatogenesis in adult testes could ...

Pancreatic beta-cell apoptosis is known to participate in the beta-cell destruction process that occurs in diabetes. A better understanding of how it takes place is essential for future development of therapeutic strategies aimed at preventing beta-cell loss and diabetes. In this study we determine the possible role that high glucose ...

The clinical use of doxorubicin, a highly active anticancer drug, is limited by its severe cardiotoxic side effects. Increased oxidative stress and apoptosis have been implicated in the cardiotoxicity of doxorubicin. Carvedilol is an adrenergic blocking agent with potent anti-oxidant activity. In this study we investigated whether carvedilol has protective ...

Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that ...