Search results for "DAMAGE"
showing 10 items of 1289 documents
Microvascular brain damage with aging and hypertension
2011
Loss of cognitive function and hypertension are two common conditions in the elderly and both significantly contribute to loss of personal independency. Microvascular brain damage - the result of age-associated alteration in large arteries and the progressive mismatch of their cross-talk with small cerebral arteries - represents a potent risk factor for cognitive decline and for the onset of dementia in older individuals. The present review discusses the complexity of factors linking large artery to microvascular brain disease and to cognitive decline and the evidence for possible clinical markers useful for prevention of this phenomenon. The possibility of dementia prevention by cardiovasc…
Exposure to gp120 of HIV-1 induces an increased release of arachidonic acid in rat primary neuronal cell culture followed by NMDA receptor-mediated n…
1995
After incubation of highly enriched neurons from rat cerebral cortex with the HIV-1 coat protein gp120 for 18 h, cells showed fragmentation of DNA at internucleosomal linkers followed by NMDA receptor-mediated neurotoxicity. We report that in response to exposure to gp120 cells react with an increased release of arachidonic acid (AA) via activation of phospholipase A2. This process was not inhibited by NMDA receptor antagonists. To investigate the role of AA on the sensitivity of the NMDA receptor towards its agonist, low concentrations of NMDA were co-administered with AA. This condition enhanced the NMDA-mediated cytotoxicity. Administration of mepacrine reduced cytotoxicity caused by gp1…
Pitfalls to be considered on the metabolomic analysis of biological samples by HR-MAS
2014
HR-MAS (High-Resolution Magic AngleSpinning) is considered a powerfultechnique for metabolomic studies ofbiological samples that provides “intact”tissue spectra (Cheng et al., 1998; Waterset al., 2000; Sitter et al., 2002; Martinez-Bisbal et al., 2004; Payne et al., 2006;Coen et al., 2007; Bathen et al., 2010).The performance of HR-MAS, fol-lowed by quantitative histopathology hasdemonstrated that, despite some changes,HR-MAS can preserve approximately thetissue histopathologic features producingwell-resolved spectra of cellular metabo-lites (Cheng et al., 2000). Nevertheless,therearesomeaspectsarousedintheliter-ature about the possible biochemical andstructural changes that can occur durin…
Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling
2014
The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in larg…
Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.
2014
In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose me…
Kinetics of gamma-H2AX focus formation upon treatment of cells with UV light and alkylating agents.
2008
Histone H2AX is rapidly phosphorylated in response to DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). Here we show that DNA damage induced by alkylating agents [methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] and ultraviolet light (UV-C) leads to a dose and time dependent accumulation of phosphorylated H2AX (gamma-H2AX). Time course experiments revealed that the number of gamma-H2AX foci reached peak levels 8 hr after MMS or MNNG treatment and declined to almost control values within 24 hr after exposure. Upon UV-C treatment, a biphasic response was observed with a maximum 12 hr after treatment. In 43-3B cells deficient in nucleotide excisi…
MGMT: Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents
2007
O(6)-methylguanine-DNA methyltransferase (MGMT) plays a crucial role in the defense against alkylating agents that generate, among other lesions, O(6)-alkylguanine in DNA (collectively termed O(6)-alkylating agents [O(6)AA]). The defense is highly important, since O(6)AA are common environmental carcinogens, are formed endogenously during normal cellular metabolism and possibly inflammation, and are being used in cancer therapy. O(6)AA induced DNA damage is subject to repair, which is executed by MGMT, AlkB homologous proteins (ABH) and base excision repair (BER). Although this review focuses on MGMT, the mechanism of repair by ABH and BER will also be discussed. Experimental systems, in wh…
Primary mouse fibroblasts deficient for c-Fos, p53 or for both proteins are hypersensitive to UV light and alkylating agent-induced chromosomal break…
2000
The important regulatory proteins, c-Fos and p53 are induced by exposure of cells to a variety of DNA damaging agents. To investigate their role in cellular defense against genotoxic compounds, we comparatively analysed chromosomal aberrations and apoptosis induced by ultraviolet (UV-C) light and the potent alkylating agent methyl methanesulfonate (MMS) in primary diploid mouse fibroblasts knockout for either c-Fos or p53, or double knockout for both genes. We show that c-Fos and p53 deficient fibroblasts are more sensitive than the corresponding wild-type cells as to the induction of chromosomal aberrations and apoptosis. Double knockout fibroblasts lacking both c-Fos and p53 are viable an…
AMBIENTE E TUTELA INDIVIDUALE INTERGENERAZIONALE
2020
Il saggio propone una riflessione sulla possibilità di una tutela ambientale individuale ed intergenerazionle, muovendo da una ricostruzione del concetto di ambiente nella prospettiva esistenzialista, segnata dal tessuto valoriale costituzionale interno ed europeo e dall’affermazione del principio dello sviluppo sostenibile. La valorizzazione dell’ambiente nella teoria dei beni trova nel dibattito sui beni comuni nuovi orizzonti di senso, coniugando la prospettiva esistenzialista del danno ambientale con quella propria della teorica dei beni comuni. All’esito di tale percorso ricostruttivo, avvalorato dalle recenti pronunce della Corte europea, l’autore giunge a fondare una legittimazione i…
Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors
1998
PURPOSE:To examine the apoptotic effect induced in human retinoblastoma Y79 cells by camptothecin, etoposide, and amsacrine, to examine the effect of these drugs on the expression of many apoptosis-related modulators, and to test the antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:Morphologic features of apoptosis were demonstrated using acridine orange- ethidium bromide staining and electron microscopy. DNA fragmentation was determined by means of an in situ cell detection procedure (TdT-dUTP terminal nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was quantified by enzyme-linked immunosorbent assay. The expression of apoptosis-related mod…