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Triggers Cell Death (trigger + cell_death)
Selected AbstractsDissolved copper triggers cell death in the peripheral mechanosensory system of larval fishENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Tiffany L. Linbo Abstract Dissolved copper is an increasingly common non,point source contaminant in urban and urbanizing watersheds. In the present study, we investigated the sublethal effects of dissolved copper on the peripheral mechanosensory system, or lateral line, of larval zebrafish (Danio rerio). Zebrafish larvae were exposed to copper (0,65 ,g/L), and the cytotoxic responses of individual lateral line receptor neurons were examined using a combination of in vivo fluorescence imaging, confocal microscopy, scanning electron microscopy, and conventional histology. Dissolved copper triggered a dose-dependent loss of neurons in identified lateral line neuromasts at concentrations ,20 ,g/L. The onset of cell death in the larval mechanosensory system was rapid (<1 h). When copper-exposed zebrafish were transferred to clean water, the lateral line regenerated over the course of 2 d. In contrast, the lateral line of larvae exposed continuously to dissolved copper (50 ,g/L) for 3 d did not recover. Collectively, these results show that peripheral mechanosensory neurons are vulnerable to the neurotoxic effects of copper. Consequently, dissolved copper in non-point source storm-water runoff has the potential to interfere with rheotaxis, schooling, predator avoidance, and other mechanosensory-mediated behaviors that are important for the migration and survival of fish. [source] Degradable, Surfactant-Free, Monodisperse Polymer-Encapsulated Emulsions as Anticancer Drug CarriersADVANCED MATERIALS, Issue 18 2009Sri Sivakumar Anticancer emulsions: Degradable, surfactant- free, micrometer- to sub-micrometer-sized polymer-encapsulated emulsions loaded with lipophilic drugs (doxorubicin and 5-fluorouracil) are prepared. In vitro drug-release studies demonstrate controlled release under redox conditions and incubation with human colorectal cancer cells triggers cell death with greater efficiency (,106 fold) than the free drug. [source] Mitotic catastrophe and apoptosis induced by docetaxel in hormone-refractory prostate cancer cells,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Francesco Fabbri Studies performed in different experimental and clinical settings have shown that Docetaxel (Doc) is effective in a wide range of tumors and that it exerts its activity through multiple mechanisms of action. However, the sequence of events induced by Doc which leads to cell death is still not fully understood. Moreover, it is not completely clear how Doc induces mitotic catastrophe and whether this process is an end event or followed by apoptosis or necrosis. We investigated the mechanisms by which Doc triggers cell death in hormone-refractory prostate cancer cells by analyzing cell cycle perturbations, apoptosis-related marker expression, and morphologic cell alterations. Doc induced a transient increase in G2/M phase followed by the appearance of G0/1 hypo- and hyperdiploid cells and increased p21 expression. Time- and concentration-dependent apoptosis was induced in up to 70% of cells, in concomitance with Bcl-2 phosphorylation, which was followed by caspase-2 and -3 activation. In conclusion, Doc would seem to trigger apoptosis in hormone-refractory prostate cancer cells via mitotic catastrophe through two forms of mitotic exit, in concomitance with increased p21 expression and caspase-2 activation. J. Cell. Physiol. 217: 494,501, 2008. © 2008 Wiley-Liss, Inc. [source] Selective vulnerability in Alzheimer's disease: Amyloid precursor protein and p75NTR interaction,ANNALS OF NEUROLOGY, Issue 3 2009Joanna Fombonne PhD Objective Selective neuronal vulnerability in neurodegenerative diseases is poorly understood. In Alzheimer's disease, the basal forebrain cholinergic neurons are selectively vulnerable, putatively because of their expression of the cell death mediator p75NTR (the common neurotrophin receptor), and its interaction with proapoptotic ligands pro,nerve growth factor and amyloid-, peptide. However, the relation between amyloid precursor protein (APP) and p75NTR has not been described previously. Methods APP and p75NTR were assayed for interaction by coimmunoprecipitation in vitro and in vivo, yeast two-hybrid assay, bioluminescence resonance energy transfer, and confocal microscopy. Effects on APP processing and signaling were studied using immunoblotting, enzyme-linked immunosorbent assays, and luciferase reporter assays. Results The results of this study are as follows: (1) p75NTR and APP interact directly; (2) this interaction is modified by ligands nerve growth factor and ,-amyloid; (3) APP and p75NTR colocalization in vivo is modified in Alzheimer's model transgenic mice; (4) APP processing is altered by p75NTR, and to a lesser extent, p75NTR processing is altered by the presence of APP; (5) APP-dependent transcription mediated by Fe65 is blocked by p75NTR; and (6) coexpression of APP and p75NTR triggers cell death. Interpretation These results provide new insight into the emerging signaling network that mediates the Alzheimer's phenotype and into the mechanism of basal forebrain cholinergic neuronal selective vulnerability. In addition, the results argue that the interaction between APP and p75NTR may represent a therapeutic target in Alzheimer's disease. Ann Neurol 2009;65:294,303 [source] | ||||||||||