Search results for "cell cycle."
showing 10 items of 803 documents
Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells.
2000
Proteolysis mediated by the ubiquitin-proteasome system has been implicated in the regulation of programmed cell death. Here we investigated the differential effects of proteasomal inhibitors on the viability of proliferating and quiescent primary endothelial cells in vitro and in vivo. Subconfluent, proliferating cells underwent carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI) -induced apoptosis at low concentrations (EC(50)=24 nM), whereas at least 340-fold higher concentrations of PSI were necessary to obtain the same effect in confluent, contact-inhibited cells. PSI-mediated cell death could be blocked by a caspase-3 inhibitor (Ac-DEVD-H), but not by a caspase…
Effect of ultraviolet light, methyl methanesulfonate and ionizing radiation on the genotoxic response and apoptosis of mouse fibroblasts lacking c-Fo…
2001
c-Fos and p53 are DNA damage-inducible proteins that are involved in gene regulation, cell cycle checkpoint control and cell proliferation following exposure to genotoxic agents. To investigate comparatively the role of c-Fos and p53 in the maintenance of genomic stability and the induction of apoptosis, we generated mouse fibroblast cell lines from knockout mice deficient for either c-fos (fos -/-) or p53 (p53-/-) or for both gene products (fosp53-/-). The sensitivity of these established cell lines was compared with the corresponding wild-type cells as to the cytotoxic, clastogenic and apoptosis-inducing effects of ultraviolet (UV-C) light and methyl methanesulfonate (MMS). Additionally, …
On Cancer Cell Cycle and Universal Apoptosis Parameters Signaling Unravelled In Silico
2010
Here, cell cycle in higher eukaryotes and their molecular networks signals both in G1/S and G2/M transitions are in silico replicated. Systems control theory is employed to design multi-nestled digital layers to simulate protein-to- protein activation and inhibition in the cancer cell cycle dynamics in presence of damaged genome. Sequencing and controlling the digital process of four micro-scale species networks (p53/Mdm2/DNA damage; p21mRNA/cyclin-CDK complex; CDK/CDC25/wee1/SKP2/APC/CKI and apoptosis target genes system) paved the way for unravelling the participants and their by-products having the task to execute (or not) cell death. The results of the proposed cell digital multi-layers…
Highlighting curcumin-induced crosstalk between autophagy and apoptosis: A biochemical approach coupling impedancemetry, imaging, and flow cytometry
2019
Curcumin, a major active component of turmeric (Curcuma longa, L.), is known to have various effects on both healthy and cancerous tissues. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying the anticancer effects of curcumin is still unclear. Since there is a consensus about endoplasmic reticulum (ER) stress being involved in the cytotoxicity of many natural compounds, we investigated by Amnis ® Imaging flow cytome-try the mechanistic aspects of curcumin's destabilization of the ER, but also the status of the lysosomal compartment involved in curcumin-associated apoptosis. Curcumin induces ER stress thereby causing an un…
DNA Damage Response and the Balance Between Cell Survival and Cell Death
2009
DNA damage induces the activation of a cascade of kinases that trigger the DNA damage response (DDR). Downstream are targets that either help cells to survive or undergo cell death. DNA damage-induced cell death is executed by apoptosis, necrosis, mitotic catastrophe, and autophagy. Of these different forms of cell inactivation, apoptosis is often the main route of cell death following DNA damage. Cells undergo apoptosis upon genotoxic stress via the death receptor and/or the intrinsic mitochondrial damage pathway, with p53 and AP-1 involved decisively. Not every type of DNA damage induces apoptosis. Many DNA lesions are tolerated by the cell, some are mutagenic without being toxic and some…
Silymarin and Cancer: A Dual Strategy in Both in Chemoprevention and Chemosensitivity
2020
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemor…
The human first cell cycle: impact on implantation.
2013
The morphology of fertilization events has been related to successful implantation by subjective criteria (pronuclei score, pronuclei symmetry and position). This work first described these events by time-lapse technology and then compared the timings of fertilization events (second polar body extrusion, first and second pronuclei appearance, abuttal and fading) in implanted versus nonimplanted embryos in a 2-year cohort retrospective study. A total of 1448 transferred embryos from 842 patients undergoing intracytoplasmic sperm injection with oocyte donation were monitored, 212 embryos from treatments where the number of gestational sacs matched the number of transferred embryos and 687 emb…
Microtubules and the First Cell Cycle in Cultured Mesophyll Protoplasts of Nicotiana
1990
When a protoplast is excised and cultured in vitro, an organized pattern of cell divisions must be reestablished to permit organogenesis, including plant regeneration. However, in a number of species protoplasts have proved to be very recalcitrant with regard to cell division and/or plant regeneration. In an attempt to find means to overcome the regeneration problem in recalcitrant species we are investigating the processes leading to cell division and morphogenesis in mesophyll protoplasts of the model system Nicotiana. Of particular interest are the initiation of the cell cycle and the coordination of progress through the cycles as a prerequisite for subsequent morphogenesis. Mesophyll pr…
Cell cycle independent role of Cyclin E during neural cell fate specification in Drosophila is mediated by its regulation of Prospero function
2009
AbstractDuring development, neural progenitor cells or neuroblasts generate a great intra- and inter-segmental diversity of neuronal and glial cell types in the nervous system. In thoracic segments of the embryonic central nervous system of Drosophila, the neuroblast NB6-4t undergoes an asymmetric first division to generate a neuronal and a glial sublineage, while abdominal NB6-4a divides once symmetrically to generate only 2 glial cells. We had earlier reported a critical function for the G1 cyclin, CyclinE (CycE) in regulating asymmetric cell division in NB6-4t. Here we show that (i) this function of CycE is independent of its role in cell cycle regulation and (ii) the two functions are m…
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
2001
Glucocorticoids inhibit the proinflammatory activities of transcription factors such as AP-1 and NF-kappa B as well as that of diverse cellular signaling molecules. One of these signaling molecules is the extracellular signal-regulated kinase (Erk-1/2) that controls the release of allergic mediators and the induction of proinflammatory cytokine gene expression in mast cells. The mechanism of inhibition of Erk-1/2 activity by glucocorticoids is unknown. Here we report a novel dual action of glucocorticoids for this inhibition. Glucocorticoids increase the expression of the MAP kinase phosphatase-1 (MKP-1) gene at the promoter level, and attenuate proteasomal degradation of MKP-1, which we re…