Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzymatic procedure for the estimation of organic hydroperoxides has been adapted to biological tissues and applied to the measurement of hydroperoxides in the rat retina. Hydroperoxides are determined from the coupled activities of glutathione peroxidase and glutathione reductase as measured by the loss of NADPH absorbance. To minimize the effects of tissue catalyzed peroxide degradation, incubations were performed in the presence of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU); which inhibited the activity of retinal tissue glutathione reductase by 85%. For comparisons to the enzymatic technique, retinal tissue hydroperoxides were also estimated by the absorption of tissue extracts at 232 nm. Using the enzymatic procedure the hydroperoxide concentration in whole retina homogenates was significantly higher in 19-day-old rats than in either 35-day or adult animals. Hydroperoxides in the retina of young rats exposed to light for one hour were significantly lower than in non-exposed controls, while in adult rats, following light, hydroperoxides increased 13%. Fractionation of rat retinas into crude ROS and retina minus ROS components revealed that the ROS fractions contain at least twice the hydroperoxide concentration of the remaining retina. The concentration of hydroperoxides in the ROS fractions from dark-reared rats were significantly lower than in cyclic-light-reared animals. In both types of rats, one hour intense light exposure resulted in an increase in ROS hydroperoxides but the increases were not significant. ROS hydroperoxides were also found to be 85-90% water soluble. Estimates of the retinal hydroperoxide content obtained by absorption at 232 nm gave similar results to the enzymatic technique, but the levels were significantly lower. When retinas were maintained in vitro for one hour before analysis, hydroperoxides determined by either technique were significantly higher than in retinas assayed immediately, but A232 hydroperoxides were still significantly lower than hydroperoxides measured by the enzymatic procedure. It is concluded: (1) that the observed retinal hydroperoxide concentration depends upon animal age and the method of measurement; (2) that within the retina the photoreceptor cell contains at least a two-fold higher concentration of hydroperoxides than the remaining retina and that prior light history can affect those hydroperoxide levels (it appears that the photoreceptor cell is also a major site of hydroperoxide formation in the retina); (3) that during intense light exposure of short duration significant levels of hydroperoxides do not accumulate in the retinas of rats.
 ...
PMID:The enzymatic estimation of organic hydroperoxides in the rat retina. 683 30

We are constantly exposed, throughout life, to a wide variety of extrinsic and intrinsic agents which have the potential to damage cellular biomolecules, including DNA. Imperfections in cellular defence systems which protect against the fixation of DNA damage can lead to an accumulation of mutations which on their own, or in combination with other age-related changes, may contribute to ageing and the development of age-related pathologies. We have previously reported an increase in frequency of mutation with age in human lymphocytes taken from healthy males in the age groups, 35-39, 50-54 and 65-69 years. In this article we report on the findings of a recent study which was designed to assess whether the age-related increase in frequency of mutation was due to a decreased efficacy of the defence systems against ROS-induced DNA damage, namely antioxidant status and DNA repair processes, in the same study subjects. In vivo antioxidant status was assessed in each of the study subjects by measuring blood levels of; superoxide dismutase (SOD; EC 1.15.1.1), glutathione peroxidase (GPx; EC 1.11.1.9), catalase (EC 1.11.1.6), caeruloplasmin (CPL), uric acid and bilirubin. We did not find any statistically significant differences in the mean levels of these antioxidants between the three different age groups. To investigate the efficacy of DNA repair processes against ROS-induced DNA damage, an ELISA was used to quantitate DNA damage (as % single-stranded DNA; %SS-DNA) at various times following treatment of peripheral blood lymphocytes with hydrogen peroxide (H2O2). The results of this part of the study showed that in untreated lymphocytes, basal levels of %SS-DNA were significantly higher in individuals from the 65-69 years age group compared to the 35-39 years age group (p = 0.039, 0.0013; at 5% level of significance). No significant differences were found in H2O2 susceptibility with age immediately following treatment (p = 0.71, 1.00; at 5% level of significance) but a consistent and significant increase was observed in %SS-DNA remaining 90 min post-treatment in lymphocytes from subjects in the 65-69 years age group, compared to %SS-DNA present in lymphocytes from the 35-39 years age group (p = 0.013, 0.024; at 5% level of significance). The results of this study suggest that the age-related increase in frequency of mutations is not contributed to by alterations of in vivo antioxidant status with age but is by a decreased efficacy of the repair of ROS-induced DNA damage with age. The biological implications of somatic mutations in the ageing process are discussed.
 ...
PMID:An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. 756 67

Oxygen toxicity is an inherent challenge to aerobic life, including spermatozoa, the cells responsible for propagation of the species. How this toxicity affects the spermatozoan in its interactions with the ovum is still unknown. An increase in oxidative damage to sperm membranes, proteins, and DNA is associated with alterations in signal transduction mechanisms that affect fertility. Recent evidence suggests that spermatozoa and oocytes possess an inherent but limited capacity to generate ROS to aid in the fertilization process. Though a variety of defense mechanisms encompassing antioxidant enzymes (SOD, catalase, and GSH peroxidase and reductase), vitamins (E, C, and carotenoids), and biomolecules (GSH and ubiquinol) are available, a balance of the benefits and risks from ROS and antioxidants appears to be necessary for the survival and functioning of spermatozoa. An assay system for the evaluation of OSS needs to be developed. Such an assay will assist the clinician in the assessment of fertility status of both male and female partners. The determination of this OSS value will also theoretically identify the subgroups of responders and nonresponders to any putative antioxidant therapy. Though the therapeutic use of antioxidants appears attractive, clinicians need to be aware of exaggerated claims of antioxidant benefits by various commercial supplements for fertility purposes until proper multicenter clinical trial have been completed.
 ...
PMID:Role of oxidative stress and antioxidants in male infertility. 886 95

In vitro models based on primary cultured human chondrocytes could be useful to study the ROS-mediated inflammatory processes that seem to involve chondrocytes in vivo. In this work, we studied the enzymatic antioxidative capability of human chondrocytes removed from vertebral plates during micro-discectomy and cultured 18 days, measuring total superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) activities. We also evaluated in the same cells the amount of malondialdehyde (MDA) in order to verify the effect of the variation of the cellular enzymatic antioxidative capability on the degree of membrane lipid peroxidation. Total SOD activity increased, even if not significantly, between the 12th and the 18th day. A significant variation of GSHPx (P<0.01) and of catalase (P<0.001) activity was observed between the 3rd and the 6th day with no further variation until the 18th day. A significant increase (P<0.001) of lipid peroxidation from the 3rd to the 18th day was also observed. These results seem to indicate that only fresh human cultured chondrocytes are suitable to study, through in vitro models, the in vivo behavior of the antioxidative status of these cells.
 ...
PMID:Antioxidant enzymatic activities and lipid peroxidation in cultured human chondrocytes from vertebral plate cartilage. 970 92

The aim of this work was to provide basic data on the antioxidant defences in the annelid Eisenia fetida andrei (E. f. a.). Methods for measurement of three antioxidant enzymes-catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)-and of glutathione-S-transferase (GST) were optimized. GPX activity differed according to the substrate used: cumene hydroperoxide (CUOOH) or hydrogen peroxide (H2O2). The effects on the enzyme activities of storage up to 2 months at -80 degrees C, -20 degrees C, and +4 degrees C were evaluated. The subcellular distribution (in cytosol, mitochondrial, and microsomal fractions) was examined. The properties and subcellular distribution of the enzymes and glutathione were also characterized in dissected tissues and body fluids. The GR activity decreased at -80 degrees C and was the only one not stable at this temperature. The four enzymes were localized mainly in the cytosolic fraction. CAT distribution was unusual as it was not associated with peroxisomes, its properties being consistent with a catalase-peroxidase, rather than a true catalase. However, this result could also be an artifact linked to the use of an inappropriate method to obtain the fractions. Our observations indicate the presence of a distinct cytosolic selenium-dependent GPX (Se-GPX), and of a possible microsomal Se-GPX. A strong non-Se-GPX activity was measured in the CF and CL, which could be linked to the peroxidase activity of fetidins secreted by coelomocytes and with the ROS production of these cells. This study seems to indicate that E. f. a. is well equipped for the metabolism of electrophilic and pro-oxidants through glutathione.
 ...
PMID:Glutathione, glutathione-related enzymes, and catalase activities in the earthworm Eisenia fetida andrei. 977 78

Mitochondrial DNA (mtDNA) mutations and impaired respiratory function have been demonstrated in various tissues of aged individuals. We hypothesized that age-dependent increase of ROS and free radicals production in mitochondria is associated with the accumulation of large-scale mtDNA deletions. In this study, we first confirmed that the proportion of mtDNA with the 4977 bp deletion in human skin tissues increases with age. We then investigated the 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content in skin tissues and lipid peroxides content of the skin fibroblasts from subjects of different ages. The results showed an age-dependent increase of 8-OH-dG level in the total DNA of skin tissues of the subjects above the age of 60 years. The specific content of malondialdehyde, an end product of lipid peroxidation, was also found to increase with age. On the other hand, we examined the enzyme activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and glutathione peroxidase (GPx) in the skin fibroblasts. The activities of Cu,Zn-SOD, catalase and glutathione peroxidase were found to decrease with age. However, the activity of Mn-SOD was increased with age before 60 years but was decreased thereafter. Moreover, the activity ratios of Mn-SOD/catalase and Mn-SOD/GPx exhibited the same pattern of change with age. This indicates that free radical scavenging enzymes can effectively dispose of ROS and free radicals before 60 years of age. However, elevated oxidative stress caused by an imbalance between the production and removal of ROS and free radicals occurred in skin fibroblasts after 60 years of age. Taken together, we suggest that the functional decline of free radical scavenging enzymes and the elevation of oxidative stress may play an important role in eliciting oxidative damage and mutation of mtDNA during the human aging process.
 ...
PMID:Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin. 1002 67

Alzheimer's disease (AD) has been hypothesized to be associated with oxidative stress. In this study, the expression of key oxidative stress-handling genes was studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismutases (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GSSG-R) mRNAs, and the "marker genes" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene responses to oxidative stress can be significantly modulated by the general decrease of transcription in the AD brain. To determine if the particular oxidative stress handling gene transcription was induced or suppressed in AD, the "oxidative stress-handling gene/beta-actin" ratios were quantified and compared with control values in all brain regions studied. The Mn-SOD mRNA/beta-actin mRNA ratio was unchanged in all regions of the AD brain studied, but an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSHPx, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in cerebellum of AD patients, which may reflect the protective gene response to the increased peroxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of ROS-mediated injury rather than primary deficits of oxidative stress handling gene transcription are likely to contribute to the variable intensity of neurodegeneration in different areas of AD brain.
 ...
PMID:The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. 1009 42

Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species. Further more, growing evidence implicates cytotoxic ROS as an underlying cause in exercise-induced disturbances in muscle redox status that could result in muscle fatigue or injury. Muscle cells contain complex cellular defense mechanisms to minimize the risk for oxidative injury. Two major classes of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell: (1) enzymatic and (2) nonenzymatic antioxidants. Key antioxidant enzymes include superoxide dismutase, glutathione peroxidase, and catalase. These enzymes are responsible for removing superoxide radicals, hydrogen peroxide or organic hydroperoxides, and hydrogen peroxide, respectively. Important nonenzymatic antioxidants include vitamins E and C, beta-carotene, GSH, uric acid, ubiquinone, and bilirubin. Vitamin E, beta-carotene, and ubiquinone are located in lipid regions of the cell, whereas uric acid, GSH, and bilirubin are in aqueous compartments of the cell. Although numerous animal experiments have demonstrated that the addition of antioxidants can improve muscular performance, to date, limited evidence shows that dietary supplementation with antioxidants improves human performance. This is an important area for future research.
 ...
PMID:Antioxidants and exercise. 1041 Aug 39

Oxidant stress is associated with the generation of reactive oxygen species that are responsible for the damage of a variety of cellular components. The prevention of such biological damage can be achieved by dismutation of superoxide to H2O2 which in turn is removed by catalase and GSH peroxidase. However, redox-active iron released during the development of plasmodia in the erythrocyte can mediate the conversion of H2O2 to hydroxyl radical which is more reactive. The roles of SOD and the nitroxide SOD mimic 4-OH,2,2,6,6,tetramethyl piperidine-N-oxyl (Tempol) were examined in P. falciparum grown in vitro. Both compounds did not prevent the interference with growth inflicted by various inducers of oxidant stress. Moreover, Tempol inhibited parasite growth, in agreement with previous experiments depicting accelerated mortality in SOD overexpressing mouse model of malaria. Probably, effective defense against ROS requires balanced increments in antioxidant enzymes and is not necessarily improved by an increase in the activity of one enzyme.
 ...
PMID:The role of superoxide dismutation in malaria parasites. 1044 98

The levels of antioxidative enzymes are regulated by gene expressions as well as by post-translational modifications. Although their functions are to scavenge reactive oxygen (ROS) and nitrogen species (RNS), they may also be targets of various oxidants. When ROS and RNS modify the functions of antioxidative enzymes, especially glutathione peroxidase, they may induce apoptotic cell death in susceptible cells. It is conceivable, therefore, that at least a part of the apoptotic pathways mediated by ROS and RNS may be associated with modification of the redox regulation of cellular functions due to elevations of such substances. In this article we review recent findings about the effects of various oxidative conditions associated with alteration of these antioxidative enzymes and the concomitant cellular damage induced.
 ...
PMID:Down regulation of superoxide dismutases and glutathione peroxidase by reactive oxygen and nitrogen species. 1051 34


1 2 3 4 5 6 7 8 9 10 Next >>