Search results for "Apoptosi"
showing 10 items of 1846 documents
Short-term exposure to cadmium affects the expression of stress response and apoptosis-related genes in immortalized epithelial cells from the human …
2009
Abstract It is known that cadmium (Cd) evokes cell responses that not only involve protective reactions against toxicity but also induces cell death. Increasing interest has been recently focused on the elucidation of the cellular and molecular aspects of Cd-dependent regulation of gene expression in different model systems. Here, we examined the effects of short-term (24 h) exposure of immortalized non-tumoral HB2 cells from human breast epithelium to CdCl2 at 50 μM concentration, corresponding to the IC50 for this time of incubation. The possible occurrence of apoptosis-related events was evaluated via analysis of the physical state of the DNA and of the membrane localization of phosphaty…
Natural Products as Modulators of Apoptosis and their Role in Inflammation
2006
ABSTRACT: Modifications in apoptosis, a programmed form of cell death that participates in a wide variety of physiological processes, can contribute to many diseases, principally those associated with cell accumulation, such as inflammation. One hallmark of inflammation is the infiltration of leukocytes, which are programmed to undergo apoptosis at inflamed tissues. Resolution of inflammation thus involves the elimination of excess inflammatory cells by physiological cell death and the subsequent removal of apoptotic cells by phagocytes. Controlling this process may therefore be useful in the treatment of pathologies, which include an inflammatory component. Interestingly, while in some cas…
GD3 ganglioside directly targets mitochondria in a bcl-2-controlled fashion.
2000
Lipid and glycolipid diffusible mediators are involved in the intracellular progression and amplification of apoptotic signals. GD3 ganglioside is rapidly synthesized from accumulated ceramide after the clustering of death-inducing receptors and triggers apoptosis. Here we show that GD3 induces dissipation of DeltaPsim and swelling of isolated mitochondria, which results in the mitochondrial release of cytochrome c, apoptosis inducing factor, and caspase 9. Soluble factors released from GD3-treated mitochondria are sufficient to trigger DNA fragmentation in isolated nuclei. All these effects can be blocked by cyclosporin A, suggesting that GD3 is acting at the level of the permeability tran…
Insulin and IGFs induce apoptosis in chick embryo retinas deprived of L-glutamine
1999
In chick embryo retinas, cultured in serum-free medium lacking L-glutamine, IGF-I, IGF-II and insulin induced apoptotic DNA fragmentation and cell death, IGF-I being the most efficacious compound. The apoptotic effect, which was particularly evident in retinas removed from 7-day-old chick embryos, declined with the age of the embryos and disappeared after day 11. Apoptosis appeared after a time lag of 8 h and then increased with time up to 16 h. Cycloheximide, an inhibitor of protein synthesis, was capable of entirely abolishing apoptotic cell death. The effect induced by IGFs or insulin was suppressed by the addition of glutamine. Cytokine-mediated apoptosis was also observed after withdra…
Novel ways to sensitise gastrointestinal cancer to apoptosis.
2009
Gastrointestinal (GI) cancers are major health problems, being the most common cancers worldwide. Resistance to apoptosis is closely linked to carcinogenesis and enables malignant cells to evade therapy-induced cell death. In the recent past, the increasing understanding of molecular pathways of apoptosis has provided novel targets in cancer therapy. Several drugs, either inhibiting antiapoptotic signalling or actively inducing apoptosis in cancer cells, have already entered clinical trials. Until now, agents targeting apoptosis pathways are primarily being tested alone or in combination with chemotherapy. In the near future, personalized combination therapies will probably be beneficial fo…
Therapeutic targeting of apoptotic pathways in cancer.
2006
Programmed cell death (apoptosis) is a key tumor suppressor mechanism. Consequently, most if not all cancers develop mechanisms to abolish or circumvent this genetic program. Besides enabling malignant transformation and tumor progression, defects in apoptosis can result in resistance to cytotoxic cancer therapies. Much progress has been made in the delineation of the molecular pathways leading to apoptosis. This allows the identification of target molecules and lead compounds to develop novel therapies, which make use of this intrinsic death program for the treatment of cancer. Here, we review the current understanding of apoptotic signal transduction pathways, and strategies of their ther…
Glutathione in Cancer Biology and Therapy
2006
The glutathione (GSH) content of cancer cells is particularly relevant in regulating mutagenic mechanisms, DNA synthesis, growth, and multidrug and radiation resistance. In malignant tumors, as compared with normal tissues, that resistance associates in most cases with higher GSH levels within these cancer cells. Thus, approaches to cancer treatment based on modulation of GSH should control possible growth-associated changes in GSH content and synthesis in these cells. Despite the potential benefits for cancer therapy of a selective GSH-depleting strategy, such a methodology has remained elusive up to now. Metastatic spread, not primary tumor burden, is the leading cause of cancer death. Fo…
Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activi…
2009
Oxysterols resulting from spontaneous or enzymatic oxidation of cholesterol are present in numerous foodstuffs and have been identified at increased levels in the plasma and the vascular walls of patients with cardiovascular diseases, especially in atherosclerotic lesions. Consequently, their role in lipid disorders is widely suspected, but they may also contribute to the development of important degenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, osteoporosis, age-related macular degeneration, and cataract. Since these pathologies can be associated with the presence of apoptotic cells, oxidative and inflammatory processes, and lipid disorders, the ab…
Control of Programmed Cell Death by Distinct Electrical Activity Patterns
2010
Electrical activity and sufficient supply with survival factors play a major role in the control of apoptosis in the developing cortex. Coherent high-frequency neuronal activity, which efficiently releases neurotrophins, is essential for the survival of immature neurons. We studied the influence of neuronal activity on apoptosis in the developing cortex. Dissociated cultures of the newborn mouse cerebral cortex were grown on multielectrode arrays to determine the activity patterns that promote neuronal survival. Cultures were transfected with a plasmid coding for a caspase-3-sensitive fluorescent protein allowing real-time analysis of caspase-3-dependent apoptosis in individual neurons. Ele…
Temporospatial expression of HSP72 and c-JUN, and DNA fragmentation in goat hippocampus after global cerebral ischemia
2001
The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischemia. The animals were subjected to 20-min ischemia (bilateral occlusion of the external carotid arteries plus bilateral jugular vein compression) and allowed to reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion. However, such an ischemic insult produced extensive, selective, and delayed degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days, but…