Search results for "Superoxide"

One Enzyme, Two Functions

2010

The human enzyme paraoxonase-2 (PON2) has two functions, an enzymatic lactonase activity and the reduction of intracellular oxidative stress. As a lactonase, it dominantly hydrolyzes bacterial signaling molecule 3OC12 and may contribute to the defense against pathogenic Pseudomonas aeruginosa. By its anti-oxidative effect, PON2 reduces cellular oxidative damage and influences redox signaling, which promotes cell survival. This may be appreciated but also deleterious given that high PON2 levels reduce atherosclerosis but may stabilize tumor cells. Here we addressed the unknown mechanisms and linkage of PON2 enzymatic and anti-oxidative function. We demonstrate that PON2 indirectly but specif…

Long term p38-a deficiency up-regulates antioxidant enzymes through compensatory NF-?B activation

2015

p38a MAPK may function as a mediator of reactive oxygen species signaling and thus p38a is considered a sensor of oxidative stress. In liver-specific p38a knock-out (KO) adult mice we previously found glutathione depletion and down-regulation of antioxidant enzymes. Our aim was to assess the influence of long-term p38a deficiency on oxidative stress and on the regulation of antioxidant enzymes in liver of old mice. To this end, wild type or liver-specific KO mice after weaning, at 4-6 months of age, or at 24 months of age were used. Reduced glutathione (GSH) and oxidized glutathione levels were determined by mass spectrometry, gene expression of antioxidant enzymes was determined by RT-PCR,…

Uncoupling of Endothelial Nitric Oxide Synthase in Cardiovascular Disease and its Pharmacological Reversal

2010

Publisher Summary This chapter discusses the role of oxidative stress in vascular dysfunction and atherogenesis, and strategies for its prevention. Endothelial dysfunction and oxidative stress have been identified as a common denominator of many cardiovascular risk factors. They support pro-inflammatory, prothrombotic, proliferative, and vasoconstrictor mechanisms that are involved in the initiation, progression, and complications of atherosclerosis. The pathophysiologic causes of oxidative stress involve changes in a number of different enzyme systems. Increased production of ROS by uncoupled eNOS is likely to contribute significantly to vascular oxidative stress and endothelial dysfunctio…

Synthesis of .beta.-ionone in an aldehyde/xanthine oxidase/.beta.-carotene system involving free radical formation

1994

The enzymic cooxidation of β-carotene (BC) by xanthine oxidase (XO) in aqueous solutions leads to β-ionone (BI) and derivatives: epoxy-β-ionone (EPBI), dihydroactinidiolide, β-cyclocitral, pseudoionone, etc. We demonstrate, in this article, that this is due to free radical (R . ) formation during the first hour of stirring and the use of aldehydes as substrate. The bleaching of BC does not occur when the common substrate of XO, xanthine, is used; this proves that the superoxide anion O 2 .- alone is not active on BC. BI formation in this case is not observed

Chronic Lymphocytic Leukemia: Correlations Between Oxidative Stress Metabolism and Cytogenetic Subgroups

2008

Abstract The chronic lymphocytic leukemia (B cell-CLL) is a heterogeneous lymphoproliferative disorder susceptible to oxidative stress. The excessive production of reactive oxygen intermediates above the capability of naturally produced antioxidants may result in the instability of essential macromolecules, and represents the molecular basis of many diseases including cancer. Highly reactive radicals interact with DNA inducing a multitude of oxidative modifications, and are implicated in mutagenesis due to misreplication of the damaged base 8-oxo-2′-deoxiguanosine (8-oxo-dG). Furthermore, protooncogene activation and/or tumor suppressor gene inhibition has been reported as a consequence of …

Oxidative stress and enzymatic antioxidant mechanisms in essential hypertension

2001

Age-related changes in antioxidant status and oxidative damage to lipids and dna in mitochondria of rat liver

2005

To investigate the correlation between oxidative stress and mitochondrial damage with aging, antioxidant system, levels of oxidative DNA damage and as an index of the loss of plasma membrane integrity lipid peroxidation and membrane potential were studied. Results showed that the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase significantly decreased during aging, however glutathione peroxidase (GSH-PX) increased in the aged mitochondria and glutathione (GSH) did not change during aging. No statistical difference was observed in the lipid peroxidation of mitochondria between young and old animals. The level of oxidative DNA damage (measured as 8oxo-dG) tended to in…

Sex Differences in Mitochondrial Antioxidant Gene Expression

2020

Females live longer than males. This could be in part due to the higher levels of estrogens in females, which protect them against aging. Physiological concentrations of estrogens have antioxidant effects as they induce the expression of manganese superoxide dismutase and glutathione peroxidase by stimulating estrogen receptors and the mitogen-activated protein kinase and nuclear factor kappa B pathways. However, estrogens can have undesirable effects such as they are feminizing to males, so other alternatives need to be searched. Phytoestrogens are good candidates as they can also bind to estrogens receptors, and in fact, they are able to mimic the antioxidant properties of estrogens. It i…

Exercise as an antioxidant: it up-regulates important enzymes for cell adaptations to exercise

2006

Abstract Aims. – To assess the role of the reactive oxygen species (ROS) in cell signalling and in the regulation of gene expression. Methods. – Exercise causes oxidative stress only when exhaustive. Strenuous exercise causes oxidation of glutathione, release of cytosolic enzymes, and other signs of cell damage. We have tested this hypothesis by studying the effect of inhibition of ROS production by allopurinol (an inhibitor of xanthine oxidase, a free radical generating enzyme) on cell signalling pathways in marathon runners and in rats submitted to exhaustive exercise by running on a treadmill. Results. – Exercise caused an activation of NF-κB in lymphocytes from marathon runners which wa…

Implication of eNOS Uncoupling in Cardiovascular Disease

2017

Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial nitric oxide synthase (eNOS). Endothelial NO relaxes blood vessels, inhibits platelet activity, and protects against atherosclerosis. Under pathological conditions such as hypertension, diabetes, and hypercholesterolemia, eNOS may become uncoupled. Uncoupled eNOS generates superoxide at the expense of NO and contributes substantially to oxidative stress and endothelial dysfunction. Major mechanisms of eNOS uncoupling include deficiency of the eNOS cofactor tetrahydrobiopterin, deficiency of the eNOS substrate L-arginine, and eNOS S-glutathionylation. Reversal of eNOS uncoupling may rep…