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Death Programs (death + program)

Distribution by Scientific Domains
Life Sciences55%
Medical Sciences33%

Kinds of Death Programs

  • cell death program
    		•

    Selected Abstracts

    Expression of a dominant negative form of Daxx in vivo rescues motoneurons from Fas (CD95)-induced cell death

    DEVELOPMENTAL NEUROBIOLOGY, Issue 2 2005
    Cedric Raoul
    Abstract Fas-induced death of motoneurons in vitro has been shown to involve two signaling cascades that act together to execute the death program: a Fas-Daxx-ASK-1-p38 kinase-nNOS branch, which controls transcriptional and post-translational events, and the second classical Fas-FADD-caspase-8 branch. To analyze the role of Daxx in the developmental motoneuron cell death, we studied Fas-dependent cell death in motoneurons from transgenic mice that overexpress a dominant-negative form of Daxx. Motoneurons purified from these transgenic mice are resistant to Fas-induced death. This protective effect is specific to Fas because ultraviolet irradiation-triggered death is not affected by the transgene. The Daxx and the FADD pathways work in parallel because only Daxx, but not FADD, is involved in the transcriptional control of neuronal nitric oxide synthase and nitric oxide production. Nevertheless, we do not observe involvement of Daxx in developmental motoneuronal cell death, as the pattern of naturally occurring programmed cell death in vivo is normal in transgenic mice overexpressing the dominant negative form of Daxx, suggesting that Daxx-independent pathways are used during development. © 2004 Wiley Periodicals, Inc. J Neurobiol, 2005 [source]

    Coumarin A/AA induces apoptosis-like cell death in HeLa cells mediated by the release of apoptosis-inducing factor

    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2009
    Carolina Álvarez-Delgado
    Abstract It has been demonstrated that naturally occurring coumarins have strong biological activity against many cancer cell lines. In this study, we assessed the cytotoxicity induced by the naturally isolated coumarin A/AA in different cancer cell lines (HeLa, Calo, SW480, and SW620) and in normal peripheral-blood mononuclear cells (PBMCs). Cytotoxicity was evaluated using the MTT assay. The results demonstrate that coumarin A/AA was cytotoxic in the four cancer cell lines tested and importantly was significantly less toxic in PBMCs isolated from healthy donors. The most sensitive cancer cell line to coumarin A/AA treatment was Hela. Thus, the programmed cell death (PCD) mechanism induced by this coumarin was further studied in this cell line. DNA fragmentation, histomorphology, cell cycle phases, and subcellular distribution of PCD proteins were assessed. The results demonstrated that DNA fragmentation, but not significant cell cycle disruptions, was part of the PCD activated by coumarin A/AA. Interestingly, it was found that apoptosis-inducing factor (AIF), a proapoptotic protein of the mitochondrial intermembrane space, was released to the cytoplasm in treated cells as detected by the western blot analysis in subcellular fractions. Nevertheless, the active form of caspase-3 was not detected. The overall results indicate that coumarin A/AA induces a caspase-independent apoptotic-like cell death program in HeLa cells, mediated by the early release of AIF and suggest that this compound may be helpful in clinical oncology. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:263,272, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20288 [source]

    Contribution of a mitochondrial pathway to excitotoxic neuronal necrosis

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2009
    Dae-Won Seo
    Abstract It is traditionally thought that excitotoxic necrosis is a passive mechanism that does not require the activation of a cell death program. In this study, we examined the contribution of the cytochrome c-dependent mitochondrial death pathway to excitotoxic neuronal necrosis, induced by exposing cultured cortical neurons to 1 mM glutamate for 6 hr and blocked by the NMDA antagonist, dizocilpine. Glutamate treatment induced early cytochrome c release, followed by activation of caspase-9 and caspase-3. Preincubation with the caspase-9 inhibitor z-LEHD-fmk, the caspase-3 inhibitor z-DEVD-fmk, or the specific pan-caspase inhibitor Q-VD-oph decreased the percentage of propidium iodide-positive neurons (52.5% ± 3.1%, 39.4% ± 3.5%, 44.6% ± 3%, respectively, vs. 65% ± 3% in glutamate + vehicle). EM studies showed mitochondrial release of cytochrome c in neurons in the early stages of necrosis and cleaved caspase-3 immunoreactivity in morphologically necrotic neurons. These results suggest that an active mechanism contributes to the demise of a subpopulation of excitotoxic necrotic neurons. © 2009 Wiley-Liss, Inc. [source]

    Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: A new strategy in anti-apoptotic drug discovery

    MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 1 2009
    Valerian E. Kagan
    Abstract Thre 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 regulation of components of mitochondrial antioxidant system such as Mn-SOD demonstrated significant antitumor efficiency, particularly in combination therapy. This review is focused on a newly discovered early stage of mitochondria-dependent apoptosis , oxidative lipid signaling involving a mitochondria-specific phospholipid cardiolipin (CL). Cytochrome c (cyt c) acts as a CL-specific peroxidase very early in apoptosis. At this stage, the hostile events are still secluded within the mitochondria and do not reach the cytosolic targets. CL oxidation process is required for the release of pro-apoptotic factors into the cytosol. Manipulation of cyt c interactions with CL, inhibition of peroxidase activity, and prevention of CL peroxidation are prime targets for the discovery of anti-apoptotic drugs acting before the "point-of-no-return" in the fulfillment of the cell death program. Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery. [source]

    Neuroprotective Strategies to Avert Seizure-Induced Neurodegeneration in Epilepsy

    EPILEPSIA, Issue 2007
    Janice R. Naegele
    Summary:, Neurodegeneration in limbic circuits is a hallmark feature of chronic temporal lobe epilepsy (TLE). Studies in experimental animal models and human patients indicate that seizure-induced neuronal injury involves some active, as well as passive cell death processes. Experimental approaches that inhibit active steps in cell death programs have been shown to reduce neuronal cell death and sclerosis, but not to prevent epileptogenesis in animal models of TLE. These findings suggest that we need additional research using both animal models and brain slices from human patients to understand the pathological mechanisms underlying seizure generation. Such comparative studies will also aid in evaluating the potential therapeutic value of inhibiting cell death in seizure disorders. [source]

    Multiple cell death programs: Charon's lifts to Hades

    FEMS YEAST RESEARCH, Issue 2 2004
    Wilfried Bursch
    Abstract Cells use different pathways for active self-destruction as reflected by different morphology: while in apoptosis (or "type I") nuclear fragmentation associated with cytoplasmic condensation but preservation of organelles is predominant, autophagic degradation of cytoplasmic structures preceding nuclear collapse is a characteristic of a second type of programmed cell death (PCD). The diverse morphologies can be attributed , at least to some extent , to distinct biochemical and molecular events (e.g. caspase-dependent and -independent death programs; DAP-kinase activity, Ras-expression). However, apoptosis and autophagic PCD are not mutually exclusive phenomena. Rather, diverse PCD programs emerged during evolution, the conservation of which apparently allows cells a flexible response to environmental changes, either physiological or pathological. [source]

    Chronic liver disease in murine hereditary tyrosinemia type 1 induces resistance to cell death

    HEPATOLOGY, Issue 2 2004
    Arndt Vogel
    The murine model of hereditary tyrosinemia type 1 (HT1) was used to analyze the relationship between chronic liver disease and programmed cell death in vivo. In healthy fumarylacetoacetate hydrolase deficient mice (Fah -/- ), protected from liver injury by the drug 2-(2- nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), the tyrosine metabolite homogentisic acid (HGA) caused rapid hepatocyte death. In contrast, all mice survived the same otherwise lethal dose of HGA if they had preexisting liver damage induced by NTBC withdrawal. Similarly, Fah -/- animals with liver injury were also resistant to apoptosis induced by the Fas ligand Jo-2 and to necrosis-like cell death induced by acetaminophen (APAP). Molecular studies revealed a marked up-regulation of the antiapoptotic heat shock proteins (Hsp) 27, 32, and 70 and of c-Jun in hepatocytes of stressed mice. In addition, the p38 and Jun N-terminal kinase (JNK) stress-activated kinase pathways were markedly impaired in the cell-death resistant liver. In conclusion, these results provide evidence that chronic liver disease can paradoxically result in cell death resistance in vivo. Stress-induced failure of cell death programs may lead to an accumulation of damaged cells and therefore enhance the risk for cancer as observed in HT1 and other chronic liver diseases. (HEPATOLOGY 2004;39:433,443.) [source]

    Cell death: regulation by the Bcl-2 protein family

    PSYCHOGERIATRICS, Issue 2006
    Yoshihide TSUJIMOTO
    Abstract An increase in mitochondrial membrane permeability is central to cell death including apoptosis and necrosis. During apoptosis, permeabilization of outer mitochondrial membrane leads to the release of several apoptogenic factors, such as cytochrome c and Smac/Diablo, into the cytoplasm that activate downstream death programs, including apoptotic proteases called caspases, although the detailed mechanism of outer mitochondrial membrane permeabilization remains elusive. Although the mitochondrial membrane permeability transition (MPT), resulting in ,, loss, mitochondrial swelling and rupture of the outer membrane has initially been proposed as a general mechanism for apoptotic permeabilization of outer mitochondrial membrane, the recent studies with cyclophilin D-deficient mice indicate that MPT regulates some forms of necrotic death, but not apoptotic death, and that MPT is involved in ischemia,reperfusion injury in heart and brain. Anti-apoptotic proteins, Bcl-2 and Bcl-xL, efficiently block not only apoptotic mitochondrial permeabilization but also MPT. The present paper focuses on the mechanisms by which Bcl-2 family members control the permeability of mitochondrial membrane during apoptosis and necrosis. [source]