Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h aerobic recovery on the antioxidant systems of six organs were examined in freshwater turtles, Trachemys scripta elegans. Both xanthine oxidase and xanthine dehydrogenase were detected in turtle tissues with xanthine oxidase composing 36-75% of the total activity. Turtle organs displayed high constitutive activities of catalase (CAT), superoxide dismutase (SOD), and alkyl hydroperoxide reductase (AHR). Measurements of lipid peroxidation damage products (conjugated dienes, lipid hydroperoxides, thiobarbituric acid reactive substances) showed minimal changes during anoxia or recovery suggesting that natural anoxic-aerobic transitions occur without the free radical damage that is seen during ischemia-reperfusion in mammals. Anoxia exposure led to selected decreases in enzyme activities in organs, consistent with a reduced potential for oxidative damage during anoxia: SOD decreased in liver by 30%, CAT decreased in heart by 31%, CAT and total glutathione peroxidase (GPOX) decreased in kidney (by 68 and 41%), and CAT and SOD decreased in brain (by 80 and 15%). AHR, however, increased 2 and 3.5 fold during anoxia in heart and kidney respectively. Most anoxia-induced changes were reversed during aerobic recovery although brain enzyme activities remained suppressed. Some specific changes occurred during the recovery period: SOD increased from controls in heart by 45%, AHR increased to 200 and 168% of control values in red and white muscle respectively, and total GPOX decreased from controls in heart and white muscle by 75 and 77% respectively. The results show that biochemical adaptation for natural anoxia tolerance in turtles includes well-developed antioxidant defenses that minimize or prevent damage by reactive oxygen species during the reoxygenation of organs after anoxic submergence.
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PMID:Antioxidant systems and anoxia tolerance in a freshwater turtle Trachemys scripta elegans. 914 33

Cardiac allograft vasculopathy (CAV) remains a troublesome long-term complication of heart transplantation. It is manifested by a unique and unusually accelerated form of coronary disease affecting both intramural and epicardial coronary arteries and veins.CAV is characterized by vascular injury induced by a variety of noxious stimuli, including the immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classic risk factors such as hyperlipidemia, insulin resistance, and hypertension. The obstructive vascular lesions are thought to progress through repetitive endothelial injury followed by repair response. The role of major histocompatibility complex donor-recipient differences in the pathogenesis of CAV has not yet been completely elucidated. Intracoronary ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern observed in distal segments. A lack of correlation between microvascular and epicardial vessel disease suggests discordant manifestations and progression of CAV. Apoptosis and loss of functional vascular remodeling have to be considered as important mediators of clinically relevant CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules may help prevent chronic rejection in clinical transplantation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and antiproliferative drugs may slow progression of CAV by various effects. Methods to augment endogenous nitric oxide bioavailability as well as newer immunosuppressive regimens may be protective. Balloon angioplasty has a limited role in the treatment of focal lesions. Experiences with coronary stenting, coronary artery bypass grafting, and transmyocardial laser revascularization are limited. Retransplantation has a worse outcome than initial transplantation.
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PMID:Cardiac allograft vasculopathy: a review. 932

The redox state of the carriers of electron-transport chain of cardiac mitochondria was studied in the conditions of normal perfusion, global ischemia and reoxygenation of the myocardial tissue. Experiments were performed on isolated rat hearts perfused at 37 degrees C by the "working heart" procedure. The EPR spectra of the freeze-clamped hearts were measured at 6-30 K. An analysis of the main values of g-tensor, line-shape, line-width and relaxation parameters of the components of low-temperature EPR spectra allowed to distinguish the signals from Fe-S centers of NADH-CoQ reductase and succinate-CoQ reductase, and the signals from free radical species of coenzyme Q and flavin coenzymes. The EPR spectra of hearts that were fixed during control perfusion and reperfusion contained predominantly the signal of oxidized S3 center of succinate-CoQ reductase. The free radical signal in these conditions was mainly due to ubisemiquinones. Besides the intensive signal of S3 center, the low-temperature EPR spectra contained also signals from different Fe-S centers paramagnetic in reduced state. The global ischemia of cardiac muscle caused essential reduction of the Fe-S clusters of the mitochondrial electron-transport chain. In ischemic condition the free radical EPR signal was mainly due to flavosemiquinones. The changes of the redox state of carriers of the mitochondrial respiratory chain correlated with the changes of the physiological parameters of cardiac muscle.
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PMID:[Redox state of the electron-transport carriers in cardiac mitochondria: a study by the method of low-temperature EPR spectroscopy]. 949 Jan 10

Coronary arteriosclerosis of the graft, a manifestation of CAV, continues to limit the long-term success of cardiac transplantation. It is characterized by vascular injury induced by a variety of noxious stimuli, including the humoral and cellular immune system response to the allograft, ischemia-reperfusion injury, viral infection, immunosuppressive drugs, and classical risk factors. The proliferative and obstructive vascular lesions are thought to develop through repetitive endothelial injury followed by repair response. T lymphocytes, macrophages and neutrophils migrate to the subendothelial area via the activity of endothelial adhesion molecules, and, in turn, produce various cytokines and growth factors which cause progression of the process. Development of anti-endothelial antibodies may progress CAV in specific settings. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted or de novo focal, noncircumferential plaques in proximal segments and/or a diffuse, concentric pattern of intimal proliferation observed in distal segments. In addition to the morphological alterations, functional endothelial and smooth muscle cell alterations may occur independently and transiently. The use of cyclosporine A levels > 3 mg/kg/day, HMG-CoA-reductase inhibitors and calcium antagonists has been shown to decrease the progression of CAV. Strategies for blocking T-cell costimulation and expression of adhesion molecules, cytokines and antiendothelial antibodies, as well as, antiproliferative drugs, methods to augment endogenous nitric oxide bioavailability and newer immunosuppressive regimens may be protective to endothelial injury and subsequent development of CAV. Revascularization procedures have an established, but very limited role in the setting of significant focal lesions. The ethical dilemma surrounding retransplantation, however, is considerable because of the scarcity of donor hearts.
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PMID:The continuing challenge of cardiac transplant arteriosclerosis. 980 67

Preventing the progression of established heart failure can be difficult, as multiple factors contribute to the continual decline of cardiac function. Blunting the activated neurohormonal response to a decreased systolic function is a proven means of slowing progression of CHF. Preventing further CAD and cardiac ischemia may also prove to be an effective mechanism. Two trials with HMGCoA reductase inhibitors lend support to this hypothesis. Studies using ACE inhibitors may also support this notion. Since a major portion of heart failure in the USA is caused by CAD, preventing CHF progression may be related to the prevention of CAD. Using ACE inhibitors and lipid-lowering agents, in addition to standard measures of CAD risk factor modification, may prove useful in future trials to retard the progression of heart failure. Further research and clinical trials involving this method of CHF prevention are warranted.
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PMID:Role of secondary prevention in congestive heart failure due to coronary artery disease. 989 17

Although myopathy is considered an adverse effect of treatment with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates in combined hyperlipidemia, the present study was performed to investigate whether combined hyperlipidemia itself is associated with skeletal muscle pathology and whether lipid-lowering intervention has beneficial effects. To investigate whether combined hyperlipidemia is associated with skeletal muscle pathology, 10 male patients and 15 normolipidemic controls underwent a 45-minute standardized bicycle ergometer test at a load of 2 W/kg lean body mass (parallel study). One- and 8-hour postexercise increments in the plasma level of the muscle proteins creatine kinase (CK), myoglobin (Mb), and fatty acid-binding protein (FABP) were assessed as parameters for (subclinical) skeletal muscle pathology. The 8-hour postexercise increments in CK and Mb and 1-hour postexercise increment in Mb were significantly higher in patients than in controls, thus indicating increased exercise-induced muscle membrane permeability in combined hyperlipidemia. To investigate the effects of lipid-lowering intervention on skeletal muscle in combined hyperlipidemia, 21 subjects with combined hyperlipidemia were randomized double-blindly to receive 6 weeks of treatment with fluvastatin 40 mg/d, gemfibrozil 600 mg twice daily, or combination therapy. All subjects underwent an ergometer test before and after treatment. Gemfibrozil treatment alone reduced the CK increments 8 hours postexercise by 47% and the FABP increments 1 and 8 hours postexercise by 83% and 101%, respectively (all P < .05). Combined treatment reduced Mb increments 1 hour postexercise by 54% and FABP increments 8 hours postexercise by 44% (all P < .05). A highly significant correlation existed between therapy-induced changes in plasma triglycerides and changes in postexercise increments of FABP and Mb. In conclusion, combined hyperlipidemia is associated with an increased exercise-induced release of muscle proteins, which is ameliorated by triglyceride-lowering intervention. As FABP is an indicator for ischemia-induced skeletal muscle pathology, a possible explanation is the impaired muscle blood flow during hypertriglyceridemia, which may be reversed by triglyceride-lowering intervention. The mechanism and clinical relevance of these findings remain to be investigated.
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PMID:Combined hyperlipidemia is associated with increased exercise-induced muscle protein release which is improved by triglyceride-lowering intervention. 1059 82

Arachidonic (AA) and docosahexaenoic (DHA) acids are major components of cell membranes and are of special importance to the brain and blood vessels. In utero, the placenta selectively and substantially extracts AA and DHA from the mother and enriches the fetal circulation. Studies indicate that there is little placental conversion of the parent essential fatty acids to AA and DHA. Similarly, analyses of desaturation and reductase activity have shown the placenta to be less functional than the maternal or fetal livers. There appears to be a correlation with placental size and plasma AA and DHA proportions in cord blood; therefore, placental development may be an important variable in determining nutrient transfer to the fetus and, hence, fetal growth itself. In preterm infants, both parenteral and enteral feeding methods are modeled on term breast milk. Consequently, there is a rapid decline of the plasma proportions of AA and DHA to one quarter or one third of the intrauterine amounts that would have been delivered by the placenta. Simultaneously, the proportion of linoleic acid, the precursor for AA, rises in the plasma phosphoglycerides 3-fold. An inadequate supply of AA and DHA during the period of high demand from rapid vascular and brain growth could lead to fragility, leakage, and membrane breakdown. Such breakdown would predictably be followed by peroxidation of free AA, vasoconstriction, inflammation, and ischemia with its biological sequelae. In the brain, cell death would be an extreme consequence.
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PMID:Placental delivery of arachidonic and docosahexaenoic acids: implications for the lipid nutrition of preterm infants. 1061 83

Pretreatment of dogs with simvastatin, a lipophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, increases myocardial contractile dysfunction during reperfusion after ischemia (stunning), with reduction of tissue adenosine triphosphate (ATP). This was thought to be a consequence of prevention of ubiquinone biosynthesis by the lipophilic inhibitor in the myocardial cell. We examined whether other lipophilic HMG-CoA reductase inhibitors also influence myocardial stunning in dogs. Vehicle, atorvastatin (2 mg/ kg/day), fluvastatin (4 mg/kg/day), or cerivastatin (40 microg/kg/ day) was orally administered for 3 weeks. Hydrophilic pravastatin (4 mg/kg/day) also was given. After 3 weeks, pentobarbital-anesthetized dogs were subjected to 15-min left anterior descending coronary artery occlusion followed by 2-h reperfusion. Myocardial segment function was determined by sonomicrometry. Tissue levels of ATP were determined in 2-h reperfused hearts. All inhibitors significantly decreased serum cholesterol level. The three lipophilic inhibitors resulted in a worsening of segment function in the reperfused myocardium, as compared with the vehicle group. The levels of ATP in the atorvastatin, fluvastatin, and cerivastatin groups were significantly lower than that in the vehicle group. These results confirm that lipophilic HMG-CoA reductase inhibitors enhance myocardial stunning in association with ATP reduction after ischemia and reperfusion.
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PMID:Lipophilic HMG-CoA reductase inhibitors increase myocardial stunning in dogs. 1067 58

Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.
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PMID:Heart allograft endothelial cell dysfunction. Cause, course, and consequences. 1115 95

The success of cholesterol treatment in reducing cardiovascular events has suggested addition of a cholesterol paradigm to previous clinical models of stenosis and occlusion in coronary artery disease. Risk factors for coronary artery disease now serve as guidelines for treatment goals for low-density lipoprotein cholesterol reduction. Oxidation of low-density lipoprotein cholesterol within the vessel wall initiates a variety of deleterious mechanisms contributing to atherosclerosis. Hepatic hydroxymethylglutaryl-coenzyme A reductase inhibitors or statin drugs exert a primary action on hepatic cholesterol metabolism, as well as influences on vascular reactivity, thrombus formation, inflammation, ischemia, and plaque stabilization. Trials with statin drugs have reported reduction of cardiovascular events in men and women without clinical evidence of coronary artery disease. Several trials have demonstrated angiographic stabilization with cholesterol lowering and a greater reduction in cardiovascular events, revascularization procedures, and strokes. Recent studies suggest benefits in lowering triglycerides and raising high-density lipoprotein cholesterol with drugs. A clinical approach with available cholesterol-lowering drugs is presented based on National Cholesterol Education Program guidelines and follow-up time tables. Thus, cholesterol therapy offers the opportunity to treat atherosclerotic vascular disease before, during, and after ischemic events.
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PMID:Cardiovascular basis for cholesterol therapy. 1117 84


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