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Cellular Oxidative Stress (cellular + oxidative_stress)
Selected AbstractsSSAO/VAP-1 protein expression during mouse embryonic developmentDEVELOPMENTAL DYNAMICS, Issue 9 2008Tony Valente Abstract SSAO/VAP-1 is a multifunctional enzyme depending on in which tissue it is expressed. SSAO/VAP-1 is present in almost all adult mammalian tissues, especially in highly vascularised ones and in adipocytes. SSAO/VAP-1 is an amine oxidase able to metabolise various endogenous or exogenous primary amines. Its catalytic activity can lead to cellular oxidative stress, which has been implicated in several pathologies (atherosclerosis, diabetes, and Alzheimer's disease). The aim of this work is to achieve a study of SSAO/VAP-1 protein expression during mouse embryogenesis. Our results show that SSAO/VAP-1 appears early in the development of the vascular system, adipose tissue, and smooth muscle cells. Moreover, its expression is strong in several epithelia of the sensory organs, as well as in the development of cartilage sites. Altogether, this suggests that SSAO/VAP-1 enzyme could be involved in the differentiation processes that take place during embryonic development, concretely in tissue vascularisation. Developmental Dynamics 237:2585,2593, 2008. © 2008 Wiley-Liss, Inc. [source] Chromosomal antioxidant genes have metal ion-specific roles as determinants of bacterial metal toleranceENVIRONMENTAL MICROBIOLOGY, Issue 10 2009Joe J. Harrison Summary Microbiological metal toxicity involves redox reactions between metal species and cellular molecules, and therefore, we hypothesized that antioxidant systems might be chromosomal determinants affecting the susceptibility of bacteria to metal toxicity. Here, survival was quantified in metal ion-exposed planktonic cultures of several Escherichia coli strains, each bearing a mutation in a gene important for redox homeostasis. This characterized ,250 gene,metal combinations and identified that sodA, sodB, gor, trxA, gshA, grxA and marR have distinct roles in safeguarding or sensitizing cells to different toxic metal ions (Cr2O72,, Co2+, Cu2+, Ag+, Zn2+, AsO2,, SeO32, or TeO32,). To shed light on these observations, fluorescent sensors for reactive oxygen species (ROS) and reduced thiol (RSH) quantification were used to ascertain that different metal ions exert oxidative toxicity through disparate modes-of-action. These oxidative mechanisms of metal toxicity were categorized as involving ROS and thiol-disulfide chemistry together (AsO2,, SeO32,), ROS predominantly (Cu2+, Cr2O72,) or thiol-disulfide chemistry predominantly (Ag+, Co2+, Zn2+, TeO32,). Corresponding to this, promoter- luxCDABE fusions showed that toxic doses of different metal ions up- or downregulate the transcription of gene sets marking distinct pathways of cellular oxidative stress. Altogether, our findings suggest that different metal ions are lethal to cells through discrete pathways of oxidative biochemistry, and moreover, indicate that chromosomally encoded antioxidant systems may have metal ion-specific physiological roles as determinants of bacterial metal tolerance. [source] Antioxidant Activity of Degradable Polymer Poly(trolox ester) to Suppress Oxidative Stress Injury in the CellsADVANCED FUNCTIONAL MATERIALS, Issue 1 2010Paritosh P. Wattamwar Abstract Oxidative stress is a pathological condition that has been implicated as a central player in a variety of diseases, including vascular and neurodegenerative diseases. More recently, oxidative stress has also been shown to be involved in the biological incompatibility of many materials, especially at the nanoscale. As such, there is a critical need for new biomaterials that can inhibit this response, improving the compatibility of medical devices. In this work, trolox, a synthetic antioxidant and water-soluble analogue of Vitamin E, is polymerized to form an oxidation active polymer as a new class of biomaterial. Synthesized poly(trolox ester) polymers were formulated into nanoparticles using a single emulsion technique, and their size was controlled by changing the polymer concentration in the organic solvent. Nanoparticle cytotoxicity, protective effects against cellular oxidative stress, and degradation kinetics were all evaluated. Poly(trolox ester) nanoparticles were found to have little to no cytotoxicity and were capable of suppressing cellular oxidative stress induced by cobalt nanoparticles. In vitro degradation studies of poly(trolox ester) nanoparticles indicate that the antioxidant activity of nanoparticles was derived from its enzymatic degradation to release active antioxidants. [source] Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC),HUMAN MUTATION, Issue 11 2009Eva Richard Abstract Methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC) is the most frequent genetic disorder of vitamin B12 metabolism. The aim of this work was to identify the mutational spectrum in a cohort of cblC -affected patients and the analysis of the cellular oxidative stress and apoptosis processes, in the presence or absence of vitamin B12. The mutational spectrum includes nine previously described mutations: c.3G>A (p.M1L), c.217C>T (p.R73X), c.271dupA (p.R91KfsX14), c.331C>T (p.R111X), c.394C>T (p.R132X), c.457C>T (p.R153X), c.481C>T (p.R161X), c.565C>A (p.R189S), and c.615C>G (p.Y205X), and two novel changes, c.90G>A (p.W30X) and c.81+2T>G (IVS1+2T>G). The most frequent change was the known c.271dupA mutation, which accounts for 85% of the mutant alleles characterized in this cohort of patients. Owing to its high frequency, a real-time PCR and subsequent high-resolution melting (HRM) analysis for this mutation has been established for diagnostic purposes. All cell lines studied presented a significant increase of intracellular reactive oxygen species (ROS) content, and also a high rate of apoptosis, suggesting that elevated ROS levels might induce apoptosis in cblC patients. In addition, ROS levels decreased in hydroxocobalamin-incubated cells, indicating that cobalamin might either directly or indirectly act as a scavenger of ROS. ROS production might be considered as a phenotypic modifier in cblC patients, and cobalamin supplementation or additional antioxidant drugs might suppress apoptosis and prevent cellular damage in these patients. Hum Mutat 30:1,9, 2009. © 2009 Wiley-Liss, Inc. [source] Novel neuroprotective, neuritogenic and anti-amyloidogenic properties of 2,4-dinitrophenol: The gentle face of JanusIUBMB LIFE, Issue 4 2006Fernanda G. De Felice Abstract In Roman mythology, Janus was the god of gates, doors, beginnings and endings. He was usually depicted with two faces looking in opposite directions. Janus was frequently used to symbolize change and transitions, such as the progression from past to future or from one viewpoint to another. 2,4-dinitrophenol (DNP) and other nitrophenols have long been known to be toxic at high concentrations (the 'bad' face of DNP), an effect that appears essentially related to interference with cellular energy metabolism due to uncoupling of mitochondrial oxidative phosphorylation. Five years ago, however, we published the first report showing that low concentrations of DNP protect neurons against the toxicity of the amyloid-, peptide (De Felice et al. (2001) FASEB J. 15:1297 - 1299]. Since then, other studies have provided evidence of beneficial actions of DNP (at low concentrations), including neuroprotection against different types of insult, blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal differentiation, and even extension of lifespan in certain organisms. Some of these effects appear to be due to mild mitochondrial uncoupling and prevention of cellular oxidative stress, whereas other actions are related to activation of additional intracellular signaling pathways. Thus, a novel and 'gentle' face of DNP is emerging from such studies. In this review, we discuss both toxic and beneficial actions of DNP. The evidence available so far suggests that DNP and other compounds with similar biological activities may be of significant interest to the development of novel therapeutic approaches for neurodegenerative diseases and other neurological disorders. iubmb Life, 58: 185-191, 2006 [source] Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Garth L. Nicolson Abstract Metabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that,in combination with genetic susceptibility and abdominal obesity,are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352,1369, 2007. © 2007 Wiley-Liss, Inc. [source] Mitochondrial mechanism of oxidative stress and systemic hypertension in hyperhomocysteinemiaJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2005Neetu Tyagi Abstract Formation of homocysteine (Hcy) is the constitutive process of gene methylation. Hcy is primarily synthesized by de-methylation of methionine, in which s-adenosyl-methionine (SAM) is converted to s-adenosyl-homocysteine (SAH) by methyltransferase (MT). SAH is then hydrolyzed to Hcy and adenosine by SAH-hydrolase (SAHH). The accumulation of Hcy leads to increased cellular oxidative stress in which mitochondrial thioredoxin, and peroxiredoxin are decreased and NADH oxidase activity is increased. In this process, Ca2+ -dependent mitochondrial nitric oxide synthase (mtNOS) and calpain are induced which lead to cytoskeletal de-arrangement and cellular remodeling. This process generates peroxinitrite and nitrotyrosine in contractile proteins which causes vascular dysfunction. Chronic exposure to Hcy instigates endothelial and vascular dysfunction and increases vascular resistance causing systemic hypertension. To compensate, the heart increases its load which creates adverse cardiac remodeling in which the elastin/collagen ratio is reduced, causing cardiac stiffness and diastolic heart failure in hyperhomocysteinemia. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] HIV-Tat protein induces oxidative and inflammatory pathways in brain endotheliumJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Michal Toborek Abstract Impaired function of the brain vasculature might contribute to the development of HIV-associated dementia. For example, injury or dysfunction of brain microvascular endothelial cells (BMEC) can lead to the breakdown of the blood,brain barrier (BBB) and thus allow accelerated entry of the HIV-1 virus into the CNS. Mechanisms of injury to BMEC during HIV-1 infection are not fully understood, but the viral gene product Tat may be, at least in part, responsible for this effect. Tat can be released from infected perivascular macrophages in the CNS of patients with AIDS, and thus BMEC can be directly exposed to high concentrations of this protein. To study oxidative and inflammatory mechanisms associated with Tat-induced toxicity, BMEC were exposed to increasing doses of Tat1,72, and markers of oxidative stress, as well as redox-responsive transcription factors such as nuclear factor-,B (NF-,B) and activator protein-1 (AP-1), were measured. Tat1,72 treatment markedly increased cellular oxidative stress, decreased levels of intracellular glutathione and activated DNA binding activity and transactivation of NF-,B and AP-1. To determine if Tat1,72 can stimulate inflammatory responses in brain endothelium in vivo, expression of monocyte chemoattractant protein-1 (MCP-1), an NF-,B and AP-1-dependent chemokine, was studied in brain tissue in mice injected with Tat1,72 into the right hippocampus. Tat1,72 markedly elevated the MCP-1 mRNA levels in brain tissue. In addition, a double immunohistochemistry study revealed that MCP-1 protein was markedly overexpressed on brain vascular endothelium. These data indicate that Tat1,72 can induce redox-related inflammatory responses both in in vitro and in vivo environments. These changes can directly lead to disruption of the BBB. Thus, Tat can play an important role in the development of detrimental vascular changes in the brains of HIV-infected patients. [source] Determination of cellular redox status by stable isotope dilution liquid chromatography/mass spectrometry analysis of glutathione and glutathione disulfideRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2008Peijuan Zhu Oxidation of glutathione (GSH) to glutathione disulfide (GSSG) occurs during cellular oxidative stress. The redox potential of the 2GSH/GSSG couple, which is determined by the Nernst equation, provides a means to assess cellular redox status. It is difficult to accurately quantify GSH and GSSG due to the ease with which GSH is oxidized to GSSG during sample preparation. To overcome this problem, a stable isotope dilution liquid chromatography/multiple reaction monitoring mass spectrometry (LC/MRM-MS) method has been developed using 4-fluoro-7-sulfamoylbenzofurazan (ABD-F) derivatization. ABD-F derivatization of the GSH thiol group was rapid, quantitative, and occurred at room temperature. The LC/MRM-MS method, which requires no sample clean-up, was validated within the calibration ranges of 5 to 400,nmol/mL in cell lysates for GSH and 0.5 to 40,nmol/mL in cell lysates for GSSG. Calibration curves prepared by adding known concentrations of GSH and GSSG to cell lysates were parallel to the standard curve prepared in buffers. GSH and GSSG concentrations were determined in two monocyte/macrophage RAW 267.4 cell lines with or without 15-LOX-1 expression (R15LO and RMock cells, respectively) after treatment with the bifunctional electrophile 4-oxo-2(E)-nonenal (ONE). R15LO cells synthesized much higher concentrations of the lipid hydroperoxide, 15(S)-hydroperoxyeicosatetraenoic acid (15-HPETE), which undergoes homolytic decomposition to ONE. GSH was depleted by ONE treatment in both RMock and R15LO cells, leading to significant increases in their redox potentials. However, R15LO cells had higher GSH concentrations (most likely through increased GSH biosynthesis) and had increased resistance to ONE-mediated GSH depletion than RMock cells. Consequently, R15LO cells had lower reduction potentials at all concentrations of ONE. GSSG concentrations were higher in R15LO cells after ONE treatment when compared with the ONE-treated RMock cells. This suggests that increased expression of 15(S)-HPETE modulates the activity of cellular GSH reductases or the transporters involved in removal of GSSG. Copyright © 2008 John Wiley & Sons, Ltd. [source] Ibuprofen and Lipoic Acid Diamides as Potential Codrugs with Neuroprotective ActivityARCHIV DER PHARMAZIE, Issue 3 2010Piera Sozio Abstract Current evidences support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, our attention was focused on ibuprofen (IBU) used in clinical trails to prevent Alzheimer's disease, and (R)-,-lipoic acid (LA) considered as a potential neuroprotective agent in AD therapy. In particular, we investigated a series of lipophilic molecular combinations obtained by joining (R)-,-lipoic acid and ibuprofen via an amide bond. These new entities might allow targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation seem related to Alzheimer's disease. Our study included the synthesis of conjugates 1,3 and the evaluation of their physicochemical and in-vitro antioxidant properties. The new compounds are extremely stable in aqueous buffer solutions (pH = 1.3 and 7.4), and in rat and human plasma they showed a slow bioconversion to ibuprofen and (R)-,-lipoic acid. Codrugs 1,3 displayed in vitro free radical scavenging activity and were hydrolyzed more rapidly in brain tissue than in rat serum indicating that these new entities might allow targeted delivery of the parent drugs to neurons. The immunohistochemical analysis of A, (1-40) protein showed that A,-injected cerebral cortices treated with ibuprofen or compound 1 showed few plaques within capillary vessels and, in particular, A, (1-40) protein was less expressed in codrug- 1 -treated than in ibuprofen-treated cerebral cortex. [source] Oxidative Stress as the Leading Cause of Acute Myocardial Infarction in DiabeticsCARDIOVASCULAR THERAPEUTICS, Issue 2 2006Clara Di Filippo ABSTRACT The risk factors, such as hypertension and metabolic syndrome, tend to promote heart pathology. These risk factors can aggravate concomitant heart insults as well. Diabetes mellitus represents one of the most important risk factors for the development of heart pathology. By itself it represents a source of vascular and heart dysfunction through formation of reactive oxygen species (ROS) and can compromise the recovery from cardiovascular diseases. This review focuses on the evidence that cellular oxidative stress is the leading cause of the worst outcome of myocardial infarction (MI) in diabetics. Hyperglycemia is viewed in this article as the primary mediator of a cascade of heart damaging events, starting from ROS formation and leading to myocardial ischemia, inflammation and death of myocytes. This article also provides insights into why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complications of myocardial infarction in diabetic patients. [source] The role of mitochondria in ageing and carcinogenesisCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2006M. A. Birch-Machin Summary Mitochondria can perform multiple cellular functions including energy production, cell proliferation and apoptosis. These organelles contain their own genetic material, mitochondrial DNA (mtDNA), which is maternally inherited. Although much smaller than the nuclear genome, mtDNA is equally important, as it has been hypothesized to play a crucial role in ageing and carcinogenesis. This is partly due to the fact that mitochondria represent the major site for the generation of cellular oxidative stress and play a key role in mediating programmed cell death (apoptosis). Damage to mtDNA is therefore an important contributor to human ageing, cancer and neurodegenerative diseases. The most relevant footprints of mtDNA damage are point mutations of single bases, or deletions of the 16.5-kb mitochondrial genome. This review will focus on the key roles of mitochondrial function and mtDNA in oxidative stress production and as a mediator of apoptosis, and on the use of mtDNA as a biomarker of sun exposure. This will be related to the contribution of mitochondria and mtDNA in the ageing process and cancer, with a specific focus on human skin. In conclusion, it is likely that the interplay between nuclear and mitochondrial genes may hold the final understanding of the mitochondrial role in these disease processes. [source] | ||||||||||||||||