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

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intermittent peri-infarct depolarizations (PID), which spread from the vicinity of the infarction over the cortex, have been reported in focal ischemia. These depolarizations resemble cortical spreading depression except that they damage the cortex and enlarge the infarct volume possibly because of compromised oxygen delivery. The main purpose of this study was to evaluate the noninvasive technique of near-infrared spectroscopy (NIRS) for the identification of PID and to evaluate its capability for further pathophysiological studies. We used male barbiturate-anesthetized Wistar rats (n = 10) in which middle cerebral artery occlusion had been performed with a surgical thread. Middle cerebral artery occlusion resulted in a drop in parietally measured regional cerebral blood flow (laser Doppler flowmetry) to 31 +/- 8% of baseline flow. Six +/- 4 minutes after the induction of focal ischemia, 5 +/- 2 direct current deflections were recorded during a one-hour measurement period which may be regarded as PID. Measuring regional cerebral blood oxygenation changes with a NIRO 500 revealed dynamic concentration changes in the three chromophores oxyhemoglobin [HbO2], deoxyhemoglobin [Hb], and the oxidized form of cytochrome aa3 [CytO] during PID. Typically, an initial slight decrease of [HbO2] (-6.1 +/- 1.7 arbitrary units [AU] and an increase of [Hb] (+11.5 +/- 7.7 AU) were followed by an increase of [HbO2] (+10.8 +/- 4.7 AU) and a decrease of [Hb] (-4.7 +/- 5.5 AU); [CytO] decreased during the depolarizations (-2.0 +/- 1.2 AU). We conclude that NIRS can detect typical PID-associated changes in blood oxygenation. We hypothesize that during the course of PID, unlike "normal" spreading depression, hypoxygenation precedes hyperoxygenation of the microcirculation in a given cortex volume as the depolarization wave propagates through hemodynamically compromised to intact tissue. This would accord with the known damaging effect of PID. The NIRS "fingerprint" of PID encourages the search for PID during early stroke in patients.
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PMID:Noninvasive near infrared spectroscopy monitoring of regional cerebral blood oxygenation changes during peri-infarct depolarizations in focal cerebral ischemia in the rat. 930 8

The effect of myocardial ischemia on mitochondrial oxidative phosphorylation was investigated using isolated, buffer-perfused rabbit hearts. After 45 min of global ischemia, oxidative phosphorylation was decreased only in the subsarcolemmal population of mitochondria with all substrates tested. The oxidation of N,N,N',N' tetramethyl p-phenylenediamine-ascorbate, an electron donor to cytochrome oxidase via cytochrome c, was decreased in subsarcolemmal mitochondria [ischemia (n = 6): 76 +/- 3 vs. control (n = 5): 105 +/- 6 nanoatoms O.min-1.mg-1, P < 0.01] but not in interfibrillar mitochondria. Only minor morphological changes were observed by electron microscopy in the isolated mitochondria after ischemia. Neither cytochrome oxidase activity measured under conditions for maximal activity nor the apparent Michaelis constant and maximum velocity values of the two cytochrome c binding sites were different in subsarcolemmal mitochondria isolated from ischemic and control hearts. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. Ischemic damage to the terminal segment of the electron transport chain involves a decrease in the content of cytochrome c, whereas the expressible catalytic activity of cytochrome oxidase remains unchanged.
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PMID:Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria. 932 48

After a brief period of global ischemia, the hippocampal CA1 region is more susceptible to irreversible damage than the paramedian neocortex. To test whether primary differences in bioenergetic parameters may be present between these regions, respiration rates and respiratory control activities were measured. In synaptosomal and nonsynaptic mitochondria isolated from the hippocampal CA1 region, state 3 respiration rates and complex IV activities were significantly lower than those present in synaptosomal and nonsynaptic mitochondria from the paramedian neocortex. These results suggest that mitochondria from the CA1 hippocampal area differ in some properties of metabolism compared with the neocortex area, which may render them more susceptible to a toxic insult such as that of ischemia. In addition, when complex I and IV activities were titrated with specific inhibitors, thresholds in ATP synthesis and oxygen respiration became apparent. Complex I and IV activities were decreased by 60% in nonsynaptic mitochondria from the hippocampal CA1 region and paramedian neocortex before oxidative phosphorylation was severely compromised; however, in synaptosomes from these regions, complex I activities had a threshold of 25%, indicating heterogenous behaviour for brain mitochondria. Reduced complex I thresholds in mitochondria, in association with other constitutive defects in energy metabolism, may induce a decreased ATP supply in the synaptic region. The implications of these findings are discussed in relation to delayed neuronal death and processes of neurodegeneration.
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PMID:Threshold effects in synaptosomal and nonsynaptic mitochondria from hippocampal CA1 and paramedian neocortex brain regions. 937 90

The purpose of this study was to test the hypothesis that hyperglycemia ameliorates changes in brain cell membrane function and preserves cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. A total of 42 ventilated piglets were divided into 4 groups, normoglycemic/normoxic(group 1, n=9), hyperglycemic/normoxic(group 2, n=8), normoglycemic/hypoxic-ischemic(group 3, n=13) and hyperglycemic/hypoxic-ischemic(group 4, n=12) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Hyperglycemia (blood glucose 350-400 mg/dl) was maintained for 90 min before and throughout hypoxia-ischemia using modified glucose clamp technique. Changes in cytochrome aa3 were continuously monitored using near infrared spectroscopy. Blood and CSF glucose and lactate were monitored. Na+, K+-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia-ischemia, glucose levels in blood and CSF were significantly elevated in hyperglycemic/hypoxic-ischemic group compared with normoglycemic/hypoxic-ischemic group, but lactate levels in blood and CSF were not different between two groups. At the end of hypoxia-ischemia of group 3 and 4, triangle up Cyt aa3, Na+, K+-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups 1 and 2, but were not different between groups 3 and 4. Levels of conjugated dienes and brain lactate were significantly increased in groups 3 and 4 compared with groups 1 and 2, and were significantly elevated in group 4 than in group 3 (0.30+/-0.11 vs. 0.09+/-0.02 micromol g-1 protein, 26.4+/-7.6 vs. 13.1+/-2.6 mmol kg-1, p<0.05). These findings suggest that hyperglycemia does not reduce the changes in brain cell membrane function and does not preserve cerebral high energy phosphates during hypoxia-ischemia in newborn piglets. We speculate that hyperglycemia may be harmful during hypoxia-ischemia due to increased levels of lipid peroxidation in newborn piglet.
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PMID:Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets. 966 46

Inspired oxygen (FiO2) was manipulated during the early reperfusion period after global cerebral ischemia (four-vessel occlusion of 20 or 30 min duration) in anesthetized rats. The goal was to determine whether oxygen availability during the early reperfusion period alters recovery of mitochondrial redox state and evoked electrical activity. The effectiveness of post-ischemic oxygen treatment was monitored at the tissue level with oxygen sensitive microelectrodes, and at the mitochondrial level by reflection spectrophotometry of the redox state of cytochrome oxidase. Transiently decreasing FiO2 from 0.3 to 0.15 limited reperfusion-induced hyperoxygenation and post-ischemic mitochondrial hyperoxidation (PIMHo). Evoked potential recovery was improved by this treatment after 20 min ischemia but not after 30 min ischemia. Increasing FiO2 from 0.3 to 1.0 exacerbated PIMHo and tissue hyperoxygenation. Transient elevation of tissue oxygen tension after 30 min of global ischemia inhibited recovery of evoked potentials. These data suggest that a period of heightened vulnerability to oxidative stress occurs within the first 10 min of reperfusion after global ischemia. This period is characterized by tissue hyperoxygenation and mitochondrial hyperoxidation. Limiting oxygen availability during this period may improve the outcome while conversely elevating oxygenation may be detrimental.
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PMID:Oxygen sensitivity of mitochondrial redox status and evoked potential recovery early during reperfusion in post-ischemic rat brain. 966 36

Using the blood-free perfused rat brain, we examined the redox behavior of cytochrome oxidase of two chromophores, heme a + a3 and copper. When perfusate inflow was stopped to induce global ischemia, the reduction of heme a + a3 was triphasic, with a rapid phase, a slow phase, and a second rapid phase. In contrast, the reduction of copper was monophasic after the rapid phase of heme a + a3. The triphasic reduction of heme a + a3 was diminished by energy-depleting treatments, such as addition of an uncoupler. The time course of the reduction of copper was not affected by the energy depletion. During global ischemia the decrease in creatine phosphate nearly paralleled the reduction of heme a + a3, whereas ATP remained at the control level until approximately 60% of heme a + a3 was reduced in the rapid phase. In the slow phase, ATP started to decrease with the reduction of copper. The redox behavior of copper was similar to the slow phase of the reduction of heme a + a3 because of the higher oxygen affinity of copper than of heme a + a3. Therefore, the rapid phase of the reduction of heme a + a3 can be used as an alarm before a decrease in ATP, whereas the reduction of copper indicates a decrease in ATP under severe hypoxia. Thus the copper signal in noninvasive near-infrared spectroscopy is a useful parameter for the clinical setting.
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PMID:Energy-dependent redox state of heme a + a3 and copper of cytochrome oxidase in perfused rat brain in situ. 975 55

The importance of mitochondria is rising as a target in pathologic processes such as ischemia. We have investigated the effects of hydrocortisone, prednisolone, dexamethasone and triamcinolone on oxidative phosphorylation, Ca2+ fluxes, swelling and membrane potentials in isolated kidney mitochondria. The measurement of respiration state 3 showed a significant decrease in presence of glucocorticoids whereas the other respiration states were not modified. When mitochondria were uncoupled and either the complexes III and IV or the complex IV were stimulated, the O2 consumption was decreased by glucocorticoids. These results suggest the cytochrome c oxidase is a target of the glucocorticoid effect on the respiratory chain. Indeed, the other mitochondrial functions investigated were unchanged, ruling out a direct effect on Ca2+ fluxes or swelling. A regulation of cytochrome c oxidase activity by glucocorticoids will be of particular interest in pathology involving metabolic insult.
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PMID:Glucocorticoids decrease cytochrome c oxidase activity of isolated rat kidney mitochondria. 975 52

Ischemic preconditioning has been shown to ameliorate injury due to subsequent ischemia in several organs. However, relatively little is known about preconditioning and the kidney. To address this, rats were randomized to control (C, N = 14), 2 min of ischemic preconditioning (P2 N = 10), 3 periods of 2 min of ischemia separated by 5 min periods of reflow (P2,3 N = 7), or three 5 min periods of ischemia separated by 5 min of reflow (P5,3 N = 6) prior to 45 min of bilateral renal ischemia followed by 24 hours of reperfusion. We observed a lower serum creatinine after 24 hours of reflow in P2, P2, 3 but not P5, 3 rats compared with C. Histology was examined in the C and P2, 3 groups and demonstrated less severe injury in the P2, 3 group. To gain insight into the mechanism by which preconditioning ameliorated ischemic injury, we performed near IR spectroscopy and 31P NMR spectroscopy. Based on near IR spectroscopy, the P2, 3 group had closer coupling of cytochrome aa3 redox state with that of hemoglobin during reflow. In the 31P NMR studies, the changes in ATP and pHi were similar during ischemia, but the P2, 3 group recovered ATP and pHi faster than C. These data suggest that ischemic preconditioning may ameliorate ischemic renal injury as assessed by functional, metabolic and morphological methods. The mechanism(s) by which this occurs requires additional study.
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PMID:Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. 1008 74

We previously reported that cardiac reperfusion results in declines in mitochondrial NADH-linked respiration. The degree of inactivation increased with age and was paralleled by modification of protein by the lipid peroxidation product 4-hydroxy-2-nonenal. To gain insight into potential sites of oxidative damage, the present study was undertaken to identify specific mitochondrial protein(s) inactivated during ischemia and reperfusion and to determine which of these losses in activity are responsible for observed declines in mitochondrial respiration. Using a Langendorff rat heart perfusion protocol, we observed age-dependent inactivation of complex I during ischemia and complex IV and alpha-ketoglutarate dehydrogenase during reperfusion. Although losses in complex I and IV activities were found not to be of sufficient magnitude to cause declines in mitochondrial respiration, an age-related decrease in complex I activity during ischemia may predispose old animals to more severe oxidative damage during reperfusion. It was determined that inactivation of alpha-ketoglutarate dehydrogenase is responsible, in large part, for observed reperfusion-induced declines in NADH-linked respiration. alpha-Ketoglutarate dehydrogenase is highly susceptible to 4-hydroxy-2-nonenal inactivation in vitro. Thus, our results suggest a plausible mechanism for age-dependent, reperfusion-induced declines in mitochondrial function and identify alpha-ketoglutarate dehydrogenase as a likely site of free radical-mediated damage.
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PMID:Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase. 1035 73

We determined the independent effects of hypoxia, glucose deprivation and ischemia (hypoxia plus glucose deprivation) on steady-state levels of mRNA coding for specific nuclear and mitochondrially encoded enzymes of oxidative metabolism in cultured rat neurons and glia. Neither hypoxia nor low glucose alone changed steady-state message levels for any transcript. However, ischemia induced a biphasic effect on mitochondrially encoded transcripts for cytochrome oxidase subunit two (CO2) and the subunits 8 and 6 of ATPase (A 8/6), initially decreasing and then increasing mRNA levels to or above the levels recorded prior to ischemia. In contrast, three nuclear encoded transcripts for mitochondrial proteins were decreased by ischemia. These data demonstrate a lack of coordination between the expression of nuclear and mitochondrial genes in the initial response to ischemia and suggest that a selective, primary reaction to brain cell insults exists within the mitochondrion.
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PMID:Ischemia induces a selective biphasic response in brain mitochondrial mRNA levels. 1038 Sep 87


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