Search results for " Damage"
showing 10 items of 1139 documents
Lack of correlation between apoptosis and DNA single-strand breaks in X-irradiated human peripheral blood mononuclear cells in the course of ageing
1998
The dependence on age of both the basal and the X-radiation-induced levels of apoptosis was examined in human peripheral blood mononuclear cells (PBMC). In the same samples, the base value and the extent of induced DNA single-strand breaks were determined, using a sensitive and fast microplate assay. PBMC were isolated from blood of donors of various age groups (20-30, 40-60 and > 70 years of age) and X-irradiated ex vivo using a 6 MV linear accelerator to give a total exposure of 4 Gy. The mean basal levels of apoptosis in PBMC from donors in the 40-60 year age group and the > 70 year age group were found to be only slightly higher (by 20-10%) compared to that of the 20-30 year age group, …
Compromised nuclear envelope integrity drives tumor cell invasion
2020
AbstractWhile mutations leading to a fragile envelope of the cell nucleus are well known to cause diseases such as muscular dystrophies or accelerated aging, the pathophysiological consequences of the recently discovered mechanically induced nuclear envelope ruptures in cells harboring no mutation are less known. Here we show that repeated loss of nuclear envelope integrity in nuclei experiencing mechanical constraints promotes senescence in nontransformed cells, and induces an invasive phenotype including increased collagen degradation in human breast cancer cells, both in vitro and in a mouse xenograft model of breast cancer progression. We show that these phenotypic changes are due to th…
DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells.
2013
Recent studies have highlighted an apparently paradoxical link between self-renewal and senescence triggered by DNA damage in certain cell types. In addition, the finding that TP53 can suppress senescence has caused a re-evaluation of its functional role in regulating these outcomes. To investigate these phenomena and their relationship to pluripotency and senescence, we examined the response of the TP53-competent embryonal carcinoma (EC) cell line PA-1 to etoposide-induced DNA damage. Nuclear POU5F1/OCT4A and P21CIP1 were upregulated in the same cells following etoposide-induced G 2M arrest. However, while accumulating in the karyosol, the amount of OCT4A was reduced in the chromatin fract…
Oxidative Stress and the Epigenetics of Cell Senescence: Insights from Progeroid Syndromes.
2019
Background: Cell senescence constitutes a critical process to respond to a variety of insults and adverse circumstances. Senescence involves the detention of DNA replication and cell proliferation, and hence, genetic programs associated with DNA damage response, chromosome stability, chromatin rearrangement, epigenetic reprogramming, and cell cycle are tightly linked to the senescent phenotype. Although senescence increases with age, the real implication of senescence regulation in the progress of aging in humans is largely discussed. In this context, reactive oxygen species (ROS) accumulation has also been postulated to play a critical role in cell homeostasis, aging processes, and contro…
Down-Regulation of Ku Autoantigen, DNA-Dependent Protein Kinase, and Poly(ADP-ribose) Polymerase during Cellular Senescence
1997
During aging and cellular senescence mutations accumulate in genomic and mitochondrial DNA. Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase have an essential role in DNA damage recognition. Our purpose was to find out whether cellular senescence of fibroblasts affects the protein components that recognize DNA damage and induce the repair process. We compared presenescent and replicatively senescent human WI-38 fibroblasts with each other and with SV-40 immortalized and serum-deficient quiescent WI-38 cells. Our results showed that replicative senescence significantly decreased the nuclear level of both p70 and p86 components of Ku autoantigen. SV-40 immortali…
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion
2021
Although mutations leading to a compromised nuclear envelope cause diseases such as muscular dystrophies or accelerated aging, the consequences of mechanically induced nuclear envelope ruptures are less known. Here, we show that nuclear envelope ruptures induce DNA damage that promotes senescence in non-transformed cells and induces an invasive phenotype in human breast cancer cells. We find that the endoplasmic reticulum (ER)-associated exonuclease TREX1 translocates into the nucleus after nuclear envelope rupture and is required to induce DNA damage. Inside the mammary duct, cellular crowding leads to nuclear envelope ruptures that generate TREX1-dependent DNA damage, thereby driving the …
The dual role of p53: DNA protection and antioxidant.
2011
The classical functions of p53 protein are those related to its role on DNA damage, cell growth arrest, senescence and apoptosis. For this reason it is called 'the guardian of the genome' and is considered one of the most important players in the development of cancer. However, more recently it has been show that p53 is not only involved in cancer, but also in ageing. p53 is stimulated by stress, which in turn results in the activation of a wide range of transcriptional targets. Low-intensity stress will activate p53 in a manner which results in antioxidant response, thus protecting against ageing because of its antioxidant function. On the contrary, high-intensity activation of p53 will re…
The role of telomeres and telomerase in the senescence of postmitotic cells
2020
Senescence is a process related to the stopping of divisions and changes leading the cell to the SASP phenotype. Permanent senescence of many SASP cells contributes to faster aging of the body and development of age-related diseases due to the release of pro-inflammatory factors. Both mitotically active and non-dividing cells can undergo senescence as a result of activation of different molecular pathways. Telomeres, referred to as the molecular clock, direct the dividing cell into the aging pathway when reaching a critical length. In turn, the senescence of postmitotic cells depends not on the length of telomeres, but their functionality. Dysfunctional telomeres are responsible for trigger…
Inspection Policies in Service of Fatigued Aircraft Structures
2011
Fatigue is one of the most important problems of aircraft arising from their nature as multiple-component structures, subjected to random dynamic loads. For guaranteeing safety, the structural life ceiling limits of the fleet aircraft are defined from three distinct approaches: Safe-Life, Fail-Safe, and Damage Tolerance approaches. The common objectives to define fleet aircraft lives by the three approaches are to ensure safety while at the same time reducing total ownership costs. In this paper, the damage tolerance approach is considered and the focus is on the inspection scheme with decreasing intervals between inspections. The paper proposes an analysis methodology to determine appropri…
Evaluation of DNA damage in murine fibroblasts treated with cigarette smoke condensate
2006
CSC is a complex chemical mixture containing about 4800 compounds, many of them have cytotoxic and mutagenic activities on mammalian cells. Most of these compounds are able to interact with DNA at different levels. Cells may respond to DNA damage by following different pathways, such as the DNA repair processes and the cell cycle and DNA damage checkpoint activation. To the aim to evaluate the biological effects of CSC on cells, alkaline comet assay and flow cytofluorimetry were used to examine DNA damage/repair and cell cycle progression. All experiments were performed by using CSC from standard cigarettes in the range of doses 30-180g/ml and Swiss 3T3 murine fibroblasts. Results obtained…