Search results for "STRESS"
showing 10 items of 6278 documents
Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal
2014
Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of the retina due to its location and metabolism. Oxidative damage has been demonstrated as a pathogenic mechanism in several retinal diseases, and reactive oxygen species are certainly important by-products of ethanol (EtOH) metabolism. Autophagy has been shown to exert a protective effect in different cellular and animal models. Thus, in our model, EtOH treatment increases autophagy flux, in a concentration-dependent manner. Mitochondrial morphology seems to be clearly altered under EtOH exposure, leading to an apparent increase in mitochondrial fission. An increase in 2′,7′-dichlorofluorescein fluorescenc…
PO-002 Angiotensin II-induced hypertension increases the mutation frequency in the rat kidney
2018
Introduction Epidemiological studies revealed an increased risk for kidney cancer in hypertensive patients. In many of these patients, the blood pressure regulating renin angiotensin aldosterone system (RAAS) is activated. A stimulated RAAS can lead to oxidative stress and DNA damage, as we have shown both in vitro and in animal models of hypertension. Here, we used a rat model to quantify mutations generated by 20 weeks of angiotensin II-infusion. Material and methods BigBlue+/- rats, which carry a transgenic lacI gene for mutation analysis, were treated with 0.4 mg angiotensin II/kg/day with the help of osmotic minipumps. Urinary samples were collected in week 15 by placing the rats into …
Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses.
2009
Udgivelsesdato: 2009-Nov Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected by phosphorylation of JNK and H2AX). In the case of resorufin no interference wit…
WIN induces apoptotic cell death in human colon cancer cells through a block of autophagic flux dependent on PPARγ down-regulation.
2014
Cannabinoids have been reported to possess anti-tumorigenic activity in cancer models although their mechanism of action is not well understood. Here, we show that the synthetic cannabinoid WIN55,212-2 (WIN)-induced apoptosis in colon cancer cell lines is accompanied by endoplasmic reticulum stress induction. The formation of acidic vacuoles and the increase in LC3-II protein indicated the involvement of autophagic process which seemed to play a pro-survival role against the cytotoxic effects of the drug. However, the enhanced lysosomal membrane permeabilization (LMP) blocked the autophagic flux after the formation of autophagosomes as demonstrated by the accumulation of p62 and LC3, two ma…
Psychological Burden in Meningioma Patients under a Wait-and-Watch Strategy and after Complete Resection Is High—Results of a Prospective Single Cent…
2020
The diagnosis of intracranial meningiomas as incidental findings is increasing by growing availability of MRI diagnostics. However, the psychological distress of patients with incidental meningiomas under a wait-and-watch strategy is unknown. Therefore, we aimed to compare the psychosocial situation of meningioma patients under wait-and-watch to patients after complete resection to bridge this gap. The inclusion criteria for the prospective monocenter study were either an incidental meningioma under a wait-and-watch strategy or no neurologic deficits after complete resection. Sociodemographic, clinical, and health-related quality of life and clinical data were assessed. Psychosocial factors…
Nupr1-Aurora Kinase A Pathway Provides Protection against Metabolic Stress-Mediated Autophagic-Associated Cell Death
2012
Abstract Purpose: The limited supply of oxygen and nutrients is thought to result in rigorous selection of cells that will eventually form the tumor. Experimental Design: Nupr1 expression pattern was analyzed in human tissue microarray (TMA) and correlated with survival time of the patient. Microarray analysis was conducted on MiaPaCa2 cells subjected to metabolic stress in Nupr1-silenced conditions. DNA repair and cell cycle–associated gene expression was confirmed by real-time quantitative PCR (qRT-PCR). Nupr1 and AURKA protective role were analyzed using RNA interference (RNAi) silencing or overexpression. DNA damage and autophagy were analyzed by Western blot analysis and immunofluoresc…
Artesunate induces oxidative DNA damage, sustained DNA double-strand breaks, and the ATM/ATR damage response in cancer cells.
2011
Abstract Artesunate, the active agent from Artemisia annua L. used in the traditional Chinese medicine, is being applied as a first-line drug for malaria treatment, and trials are ongoing that include this drug in cancer therapy. Despite increasing interest in its therapeutic application, the mode of cell killing provoked by artesunate in human cells is unknown. Here, we show that artesunate is a powerful inducer of oxidative DNA damage, giving rise to formamidopyrimidine DNA glycosylase–sensitive sites and the formation of 8-oxoguanine and 1,N6-ethenoadenine. Oxidative DNA damage was induced in LN-229 human glioblastoma cells dose dependently and was paralleled by cell death executed by ap…
The plasma membrane channel ORAI1 mediates detrimental calcium influx caused by endogenous oxidative stress.
2013
The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate-cystine antiporter system x(c)(-). GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT2…
The role of oxidative stress in apoptosis induced by the histone deacetylase inhibitor suberoylanilide hydroxamic acid in human colon adenocarcinoma …
2008
Histone deacetylase inhibitors (HDACIs) activate genes that promote cell cycle arrest and apoptosis in a number of tumor cells. This study showed that suberoylanilide hydroxamic acid (SAHA), a potent and commonly used HDACI, induced apoptosis in human colon adenocarcinoma HT-29 cells in a time- and dose-dependent manner. This effect was accompanied by the induction of oxidative stress, dissipation of mitochondrial transmembrane potential and activation of executioner caspases. Moreover, SAHA increased the levels of phosphorylated active forms of p38 and JNK. The addition of either the antioxidant N-acetylcysteine or the specific inhibitor of NADPH oxidase diphenylene iodonium chloride reduc…
Wavelength dependence of oxidative DNA damage induced by UV and visible light.
1997
DNA damage induced by UV radiation and visible light (290-500 nm) in AS52 Chinese hamster cells was analysed by an alkaline elution assay with specific repair endonucleases. Cells were exposed to extensively filtered monochrome or broad-band radiation. Between 290 and 315 nm, the ratio of base modifications sensitive to Fpg protein (i.e. 8-hydroxyguanine and formamidopyrimidines) and T4 endonuclease V (i.e. cyclobutane pyrimidine dimers) was constant (approximately 1:200), indicating that the direct excitation of DNA is responsible for both types of damage in this range of the spectrum. While the yield of pyrimidine dimers per unit dose continued to decrease exponentially beyond 315 nm, the…