Search results for "Programmed cell death"
showing 10 items of 609 documents
Loss of ATM sensitizes against O6-methylguanine triggered apoptosis, SCEs and chromosomal aberrations.
2003
A critical pre-cytotoxic and -apoptotic DNA lesion induced by methylating carcinogens and chemotherapeutic drugs is O6-methylguanine (O6MeG). The mechanism by which O6MeG causes cell death via apoptosis is only partially understood. The current model ascribes a role to DNA replication and mismatch repair, which converts O6MeG into a critical distal lesion (presumably a DNA double-strand break) that is finally responsible for genotoxicity and apoptosis. Here we analysed whether the PI3-like kinase ATM is involved in this process. ATM is a major player in recognizing and signaling DNA breaks, but most reports are limited to ionizing radiation. Comparing mouse ATM knockout fibroblasts (ATM-/-)…
Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O6-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by …
2008
Abstract O 6 -methylguanine (O 6 MeG) is a highly critical DNA adduct induced by methylating carcinogens and anticancer drugs such as temozolomide, streptozotocine, procarbazine and dacarbazine. Induction of cell death by O 6 MeG lesions requires mismatch repair (MMR) and cell proliferation and is thought to be dependent on the formation of DNA double-strand breaks (DSBs) or, according to an alternative hypothesis, direct signaling by the MMR complex. Given a role for DSBs in this process, either homologous recombination (HR) or non-homologous end joining (NHEJ) or both might protect against O 6 MeG. Here, we compared the response of cells mutated in HR and NHEJ proteins to temozolomide and…
Apoptosis in liver disease.
2006
The description of the morphological hallmarks of programmed cell death, apoptosis, in 1972 by Kerr, Wyllie and Currie started a field of research that revolutionized our understanding of cellular proliferation, tissue homeostasis and pathophysiology of many diseases. In the following years, a series of proteins involved in signaling and intracellular death pathways were identified and 30 years later the Noble Prize for physiology and medicine was awarded to S. Brenner, H. R. Horvitz and J. E. Sulston for their discoveries related to describing the mechanisms of cell death (apoptosis). The delineation of the signaling pathways that mediate apoptosis changed the paradigms of understanding in…
Characterization of cells with different mitochondrial membrane potential during apoptosis.
2005
Background Until now, the simultaneous analysis of several parameters during apoptosis, including DNA content and mitochondrial membrane potential (ΔΨ), has not been possible because of the spectral characteristics of the commonly used dyes. Using polychromatic flow cytometry based upon multiple laser and UV lamp excitation, we have characterized cells with different ΔΨ during apoptosis. Methods U937 cells were treated with the flavonoid quercetin (Qu) and stained with JC-1 to detect ΔΨ, propidium iodide (PI) for cell viability, Hoechst 33342 for DNA content, Annexin V conjugated with Alexa Fluor-647 for detection of phosphatidilserine (PS) exposure, marker of early apoptosis, or Mitotracke…
Natural and induced apoptosis during lymphocyte development in the axolotl
1999
Lymphocytes apoptosis was characterized in a urodele amphibian, the axolotl, by morphology using electron microscopy and by flow cytometry after propidium iodide staining, as well as by biochemical criteria with the detection of DNA ladders after glucocorticoid treatment. The morphological and biochemical features observed in treated axolotls are in accordance with the criteria of apoptosis found in different models of mammalian lymphocyte programmed cell death. The onset of natural apoptosis was then detected by DNA fragmentation in thymus and in spleen during lymphocyte development and ontogenesis. A typical DNA ladder characteristic of apoptosis is detectable in the thymus as early as 5 …
Caspase-dependent apoptosis during infection with Cryptosporidium parvum
1999
The protozoan parasite Cryptosporidium parvum causes persistent diarrhea and malnutrition in children and the diarrhea-wasting syndrome in AIDS. No therapy exists for eliminating the parasite in the absence of a healthy immune response. Although it had been reported that infection of intestinal cell lines with C. parvum leads to host cell death, the mechanisms of cytolysis have not been characterized. We show here that infection with C. parvum leads to typical apoptotic nuclear condensation and DNA fragmentation in host cells. Both nuclear condensation and DNA fragmentation are inhibited by a caspase inhibitor, showing that caspases are involved in this type of apoptosis. Finally, blocking …
A novel pro-apoptotic role of zinc octacarboxyphthalocyanine in melanoma me45 cancer cell's photodynamic therapy (PDT)
2018
Abstract Zn-based phthalocyanine acts as drug or photosensitizer in photodynamic therapy (PDT) for the treatment of cancer cells. The activated zinc octacarboxyphthalocyanine (ZnPcOC) reacts with oxygen, to generate reactive oxygen species for the damage of melanoma cancer cells, Me45. This in vitro study aimed at investigating the cytotoxic effects of different concentrations of ZnPcOC activated with a diode laser (λ = 685 nm) on Me45, and normal human fibroblast cells, NHDF. To perform this study 104 cells/ml were seeded in 96-well plates and allowed to attach overnight, after which cells were treated with different concentrations of ZnPcOC (10, 20 and 30 μM). After 4 h, cells were irradi…
Synthesis of Triazenoazaindoles: a New Class of Triazenes with Antitumor Activity
2011
Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many cancer types including brain, leukemia, and melanoma. A new compound class bearing a triazenoazaindole scaffold was synthesized with the aim of identifying new antiproliferative agents. Compounds 5 a-g and 6 a-c were screened against a panel of human tumor cell lines, and two of them, 5 e and 5 f, showed cytotoxicity (GI(50) range: 2.2-8.2 μM) in all cell lines. These two compou…
Role of caspase-8 in hepatocyte response to infection and injury in mice.
2007
Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the…
Influence of organophosphate poisoning on human dendritic cells.
2013
Organophosphourus compounds (OPC, including nerve agents and pesticides) exhibit acute toxicity by inhibition of acetylcholinesterase. Lung affections are frequent complications and a risk factor for death. In addition, epidemiological studies reported immunological alterations after OPC exposure. In our experiments we investigated the effects of organophosphourus pesticides dimethoate and chlorpyrifos on dendritic cells (DC) that are essential for the initial immune response, especially in the pulmonary system. DC, differentiated from the monocyte cell line THP-1 by using various cytokines (IL-4, GM-CSF, TNF-α, Ionomycin), were exposed to organophosphourus compounds at different concentrat…