Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.11.1.7 (peroxidase)
65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlamydia pneumoniae has been associated with respiratory infections and with cardiovascular disease. We describe here a patient with multi-organ failure and fatal outcome in whom C. pneumoniae was implicated as a causative agent. Serological analysis for C. pneumoniae was done by immunofluorescence. Immunohistochemistry was carried out with avidin-biotin peroxidase staining. The patient had pneumonia I month prior to death. C. pneumoniae was detected in the heart and lungs by immunohistochemistry at autopsy. The patient had an antibody pattern suggestive of current or chronic C. pneumoniae infection. Serological analysis for Legionella sp., Mycoplasma pneumoniae, CMV, EBV, enteroviral agents and markers for autoimmune disease were negative. The findings suggest C. pneumoniae as the aetiological agent in this case of multi-organ failure.
...
PMID:Chlamydia pneumoniae infection associated with multi-organ failure and fatal outcome in a previously healthy patient. 1006 59

Haptoglobin is an acute-phase protein with three major phenotypes: Hp 1-1, Hp 2-1 and Hp 2-2. Studies have shown that functional differences between these phenotypes have important consequences in a number of pathological disorders (e.g. cardiovascular disease, autoimmune disorders, infectious disease), making phenotype determination of potential use in the clinical field. Previous methods for haptoglobin phenotyping have involved electrophoresis (starch, acetate and polyacrylamide gels) with phenotype visualization by peroxidase-sensitive stains that were often carcinogenic. Less hazardous immunoblotting and isoelectric focusing procedures are also available but the methods are lengthy, expensive and often complex. Here, we describe a new method for haptoglobin phenotyping using commercially available agarose gels and a non-carcinogenic stain (3,3',5,5'-tetramethylbenzidine). Our method showed 100% agreement with starch gel electrophoresis and reliably distinguished between commercial haptoglobin phenotype standards and serum samples from patients (n = 125). We obtained a sensitivity of 0.4 g/L for all phenotypes and the gels were stable for up to 2 months. This safer and easier to use method may permit increased access to knowledge of haptoglobin phenotype, allowing improved patient management and better tailoring of treatment in a variety of clinical conditions.
...
PMID:A new method for haptoglobin phenotyping. 1050 10

The oxidative conversion of LDL into an atherogenic form is considered a pivotal event in the development of cardiovascular disease. Recent studies have identified reactive nitrogen species generated by monocytes by way of the myeloperoxidase-hydrogen peroxide-nitrite (MPO-H(2)O(2)-NO(2)(-)) system as a novel mechanism for converting LDL into a high-uptake form (NO(2)-LDL) for macrophages. We now identify the scavenger receptor CD36 as the major receptor responsible for high-affinity and saturable cellular recognition of NO(2)-LDL by murine and human macrophages. Using cells stably transfected with CD36, CD36-specific blocking mAbs, and CD36-null macrophages, we demonstrated CD36-dependent binding, cholesterol loading, and macrophage foam cell formation after exposure to NO(2)-LDL. Modification of LDL by the MPO-H(2)O(2)-NO(2)(-) system in the presence of up to 80% lipoprotein-deficient serum (LPDS) still resulted in the conversion of the lipoprotein into a high-uptake form for macrophages, whereas addition of less than 5% LPDS totally blocked Cu(2+)-catalyzed LDL oxidation and conversion into a ligand for CD36. Competition studies demonstrated that lipid oxidation products derived from 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine can serve as essential moieties on NO(2)-LDL recognized by CD36. Collectively, these results suggest that MPO-dependent conversion of LDL into a ligand for CD36 is a likely pathway for generating foam cells in vivo. MPO secreted from activated phagocytes may also tag phospholipid-containing targets for removal by CD36-positive cells.
...
PMID:Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. 1077 46

The plasma reduced glutathione (GSH) selenoperoxidase is a highly conserved enzyme. Furthermore, a small clinical study reported that patients with severe atherosclerosis had low peroxidase activities. Together these observations suggest that the peroxidase is important in preventing atherosclerosis. Yet others have reported that when the assay was run in Tris buffer, it was inactive with the concentrations of GSH found in the plasma. Second, it is known that hyperhomocysteinemia increases the rate of atherogenesis. Because there is some homology between homocysteine and the cysteine in GSH, the question is whether the hyperhomocysteinemia effect may be due to inhibition of the peroxidase. We purified the peroxidase from human plasma and determined its activity by a coupled spectrophotometric assay and a substrate disappearance chemiluminescence assay. When the peroxidase activity was determined in phosphate-buffered saline solution (PBS), there was significant activity with the reported plasma GSH concentrations (5 to 20 micromol/L). The peroxidase was exclusively in the HDL fraction. There was no correlation between the peroxidase activity and the HDL or LDL cholesterol concentrations. Finally, at physiologic concentrations of GSH (9 micromol/L), the peroxidase was inhibited by physiologic, free homocysteine concentrations (1 to 5 micromol/L). These data suggest that the peroxidase is active in vivo and may be important in protecting the endothelium from atherosclerosis by preventing oxidant injury. The homocysteine inhibition of the peroxidase suggests a possible biochemical basis for the observed association between hyperhomocysteinemia and cardiovascular disease. Our studies imply that low concentrations of this peroxidase may be an independent risk factor for atherosclerosis.
...
PMID:Physiologic concentrations of homocysteine inhibit the human plasma GSH peroxidase that reduces organic hydroperoxides. 1088 28

Atherosclerosis is a chronic inflammatory process where oxidative damage within the artery wall is implicated in the pathogenesis of the disease. Mononuclear phagocytes, an inflammatory cell capable of generating a variety of oxidizing species, are early components of arterial lesions. Their normal functions include host defense and surveillance through regulated generation of diffusible radical species, reactive oxygen or nitrogen species, and HOCl (hypochlorous acid). However, under certain circumstances an excess of these oxidizing species can overwhelm local antioxidant defenses and lead to oxidant stress and oxidative tissue injury, processes implicated in the pathogenesis of atherosclerosis. This review focuses on oxidation reactions catalyzed by myeloperoxidase (MPO), an abundant heme protein secreted from activated phagocytes which is present in human atherosclerotic lesions. Over the past several years, significant evidence has accrued demonstrating that MPO is one pathway for protein and lipoprotein oxidation during the evolution of cardiovascular disease. Multiple distinct products of MPO are enriched in human atherosclerotic lesions and LDL recovered from human atheroma. However, the biological consequences of these MPO-catalyzed reactions in vivo are still unclear. Here we discuss evidence for the occurrence of MPO-catalyzed oxidation reactions in vivo and the potential role MPO plays in both normal host defenses and inflammatory diseases like atherosclerosis.
...
PMID:Myeloperoxidase-generated oxidants and atherosclerosis. 1094 13

Risk factors for cardiovascular disease have been shown to exacerbate the inflammatory response and microvascular dysfunction that is normally associated with ischemia-reperfusion. The objective of this study was to determine whether hypercholesterolemia and/or hypertension alter I/R-induced expression of P-selectin in the intestinal vasculature. Male control and hypertensive (HTN) rats were placed on either a normal diet or high cholesterol diet (HCD) for at least 3 weeks resulting in hypercholesterolemia (HC). Ischemia was induced by occlusion of the superior mesenteric artery for 15 min, followed by either 30 min or 4 h of reperfusion. The dual radiolabeled antibody technique was used to quantify the rapid (30 min) and transcription-dependent (4 h) expression of P-selectin. Tissue myeloperoxidase (MPO) was used to quantify neutrophil infiltration. The constitutive (basal) expression of P-selectin did not differ among the experimental groups. Although I/R significantly increased P-selectin expression in control, HC, and HTN+HC, P-selectin expression did not increase in HTN. The HC group exhibited the largest increments in P-selectin expression and tissue MPO after I/R. The increment in P-selectin expression was not significantly attenuated in HC rats that were rendered thrombocytopenic with anti-platelet serum. Treatment with an anti-P-selectin antibody largely prevented the exaggerated MPO increase noted in HC. These findings indicate that hypercholesterolemia in contrast to hypertension enhances the expression of P-selectin in the postischemic intestinal vasculature.
...
PMID:Influence of hypercholesterolemia and hypertension on ischemia-reperfusion induced P-selectin expression. 1116 66

Increased LDL oxidation is associated with coronary artery disease. The predictive value of circulating oxidized LDL is additive to the Global Risk Assessment Score for cardiovascular risk prediction based on age, gender, total and HDL cholesterol, diabetes, hypertension, and smoking. Circulating oxidized LDL does not originate from extensive metal ion-induced oxidation in the blood but from mild oxidation in the arterial wall by cell-associated lipoxygenase and/or myeloperoxidase. Oxidized LDL induces atherosclerosis by stimulating monocyte infiltration and smooth muscle cell migration and proliferation. It contributes to atherothrombosis by inducing endothelial cell apoptosis, and thus plaque erosion, by impairing the anticoagulant balance in endothelium, stimulating tissue factor production by smooth muscle cells, and inducing apoptosis in macrophages. HDL cholesterol levels are inversely related to risk of coronary artery disease. HDL prevents atherosclerosis by reverting the stimulatory effect of oxidized LDL on monocyte infiltration. The HDL-associated enzyme paraoxonase inhibits the oxidation of LDL. PAF-acetyl hydrolase, which circulates in association with HDL and is produced in the arterial wall by macrophages, degrades bioactive oxidized phospholipids. Both enzymes actively protect hypercholesterolemic mice against atherosclerosis. Oxidized LDL inhibits these enzymes. Thus, oxidized LDL and HDL are indeed antagonists in the development of cardiovascular disease.
...
PMID:Oxidized LDL and HDL: antagonists in atherothrombosis. 1164 Dec 34

Oxidized low-density lipoprotein (LDL) is implicated in atherogenesis, but the mechanisms that oxidize LDL in the human artery wall have proven difficult to identify. A powerful investigative approach is mass spectrometric quantification of the oxidized amino acids that are left in proteins by specific oxidation reactions. Comparison of these molecular fingerprints in biological samples with those produced in proteins by various in vitro oxidation systems can indicate which biochemical pathway has created damage in vivo. For example, the pattern of oxidized amino acids in proteins isolated from atherosclerotic lesions implicates reactive intermediates generated by myeloperoxidase, a major phagocyte enzyme. These intermediates include hypochlorous acid, tyrosyl radical, and reactive nitrogen species, each of which generates a different pattern of stable end products. Despite this strong evidence that myeloperoxidase promotes LDL oxidation in vivo, the antioxidant that has been tested most extensively in clinical trials, vitamin E, fails to inhibit myeloperoxidase pathways in vitro. Because the utility of an antioxidant depends critically on the nature of the pathway that inflicts tissue damage, interventions that specifically inhibit myeloperoxidase or other physiologically relevant pathways would be more logical candidates for the prevention of cardiovascular disease. Moreover, levels of oxidized amino acids in urine and plasma might reflect those in tissues and therefore identify individuals with high levels of oxidative stress. Trials with such subjects would seem more likely to uncover effective antioxidant therapies than trials involving the general population.
...
PMID:Oxidized amino acids: culprits in human atherosclerosis and indicators of oxidative stress. 1203 94

Nonspecific interstitial pneumonia (NSIP) has been recognized as a separate histological classification of interstitial lung disease. Similar features are found not only in idiopathic NSIP, but also in NSIP associated with collagen vascular disorder (CVD-NSIP). We examined the clinical symptoms, laboratory findings, and prognosis of 13 cases of idiopathic NSIP and 11 cases of CVD-NSIP. Immunohistochemical staining was performed using the streptavidin/biotin/peroxidase method with anti-alpha-smooth muscle actin antibody. No differences in the distribution of clinical features, laboratory findings, and prognosis were observed between idiopathic NSIP and CVD-NSIP. In immunohistochemical staining of the fibrosing areas, myofibroblasts were observed in 7 of 13 idiopathic NSIP cases, but in 10 of 11 CVD-NSIP cases. With regards to intra-alveolar organization, myofibroblasts were observed in all 10 CVD-NSIP cases, but they were observed in only 2 of 9 idiopathic NSIP cases. We found a significantly higher myofibroblast proliferation in the intra-alveolar organization of CVD-NSIP compared to idiopathic NSIP. Clinically, idiopathic NSIP and CVD-NSIP are similar, but are pathologically different.
...
PMID:Myofibroblasts proliferation of idiopathic and collagen vascular disorders associated nonspecific interstitial pneumonia. 1276 22

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
...
PMID:The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. 1497 55


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

---