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)

Stroke-like episodes, defined as periods of acute localized neurological dysfunction during which brain imagery suggests cerebral ischemia but vascular anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal neurological deterioration and frontal hypodensities on cerebral computerized tomography (CT). Arteriography, performed in 1 patient during an acute episode, showed normal vascular anatomy. Nevertheless, capillary shunting was evident both in regions that appeared abnormal on the initial cerebral CT study and in regions that appeared normal but subsequently developed Leigh disease. Stroke-like episodes did not exacerbate systemic acidosis, and acidotic decompensations occurred independently of stroke-like episodes. In conclusion, stroke-like episodes occur in autosomal recessively inherited congenital lactic acidoses as well as in those caused by mitochondrial DNA mutations. In some cases, acute localized neurovascular changes occur in regions that subsequently develop Leigh disease.
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PMID:Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency. 1007 55

After transient cerebral ischemia in fetal sheep, delayed disruptions in cerebral energetics are represented by a delayed increase in cortical impedance, a progressive decrease in the concentration of oxidized cytochrome oxidase as measured by near-infrared spectroscopy, and cortical seizures. Because the production of nitric oxide (NO), a potent mediator of neuronal death, is increased during this phase, the present study investigated whether inhibition of NO synthesis could ameliorate the delayed disruption in cerebral energetics. Eleven late gestation fetal sheep were subjected to 30 min of transient cerebral ischemia in utero. Two hours later, the treatment group (n = 5) received a continuous infusion of N(G)-nitro-L-arginine, a competitive inhibitor of NO synthase, whereas the control group (n = 6) received PBS. Changes in concentration of oxidized cytochrome oxidase, cortical impedance, and electrocortical activity were observed for 3 d. A delayed increase in cortical impedance of similar magnitude and duration commenced at 14+/-4 h in the control and at 15+/-3 h in the treatment groups. The progressive decrease in oxidized cytochrome oxidase signal, by -2.2+/-0.2 micromol/L in the control and -2.0+/-0.4 micromol/L in the treatment group at 72 h postischemia, was similar in both groups. In both groups, delayed cortical seizures were indicated by intense low-frequency electrocortical activity. In the treatment group, duration of cortical seizures was increased and the intensity of the final electrocortical activity was more depressed (-19+/-1 dB versus -10+/-2 dB). The results indicate that after cerebral ischemia in fetal sheep, NO synthase inhibition does not ameliorate the delayed disruptions in cerebral energetics. However, the effect of NO synthase inhibition on delayed cortical seizures may improve our understanding of the role of NO during this phase.
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PMID:Nitric oxide synthase inhibition and delayed cerebral injury after severe cerebral ischemia in fetal sheep. 1040 Jan 27

It is believed that moderate hypothermia (25-32 degrees C) during cardiopulmonary bypass provides cerebral protection by reducing the cerebral metabolic rate (CMRO2). Nevertheless episodes of ischaemia do occur and thus it has been suggested that cerebral oxygenation should be monitored by jugular venous oximetry. However, this technique is cumbersome and invasive. Near infrared spectroscopy (NIRS) provides a non-invasive assessment of cerebral oxygenation and this was used together with continuousjugular venous oximetry in 21 patients undergoing hypothermic cardiopulmonary bypass. During the hypothermic period, jugular venous oximetry indicated reduced oxygen extraction consistent with a reduction in CMRO2 (increase from 61 +/- 2.5% to 74 +/- 2.5%). In contrast, near infrared spectroscopy demonstrated increased oxygen extraction (HbO2 - 11.5 +/- 1 microM, HHb + 3.2 +/- 0.3 microM) and a fall in the cerebral concentration of oxidized cytochrome oxidase ( - 1.7 +/- 0.3 microM) indicating ischaemia. These results suggest that cerebral ischaemia occurs during hypothermic cardiopulmonary bypass with a spurious rise in jugular venous oxygen saturation, which represents arterio-venous shunting. Thus if hypothermia does facilitate cerebral protection it does not appear to be a direct result of a reduction in CMRO2 and oxygen requirement.
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PMID:Does hypothermia prevent cerebral ischaemia during cardiopulmonary bypass? 1043 May 25

In this study, we tested the hypothesis that decreased cerebral perfusion pressure (CPP) induces cerebral ischemia and worsen brain damage in neonatal bacterial meningitis. Meningitis was induced by intracisternal injection of 10(9) colony forming units of Escherichia coli in 21 newborn piglets. Although CPP decreased significantly at 8 hr after bacterial inoculation, deduced hemoglobin (HbD), measured as an index of changes in cerebral blood flow by near infrared spectroscopy, did not decrease significantly. In correlation analyses, CPP showed significant positive correlation with brain ATP and inverse correlation with brain lactate levels. CPP also correlated positively with HbD and oxidized cytochrome aa3 (Cyt aa3) by near infrared spectroscopy. However, CPP did not show significant correlation with cerebral cortical cell membrane Na+,K+-ATPase activity, nor with levels of lipid peroxidation products. In summary, decreased CPP observed in this study failed to induce cerebral ischemia and further brain injury, indicating that cerebrovascular autoregulation is intact during the early phase of experimental neonatal bacterial meningitis.
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PMID:Effects of decreased cerebral perfusion pressure on cerebral hemodynamics, brain cell membrane function and energy metabolism during the early phase of experimental Escherichia coli meningitis in the newborn piglet. 1080 99

Reflection near infrared spectroscopy (reNIRS) has been proposed as a novel technique for the measurement of absolute values of total hemoglobin (tHb), oxygenated hemoglobin (oxHb), hemoglobin saturation (SO2), and cytochrome aa3 oxidation status (oxCyt aa3) in living tissue. In this study, we evaluated reNIRS during physiological cerebral blood flow conditions in rats (n=6) and during the induction of global cerebral ischemia in gerbils (n=6). ReNIRS parameters were assessed over the exposed cerebral cortex and compared to regional cerebral blood flow (rCBF) data obtained by laser Doppler flowmetry. Under physiological conditions, reNIRS measurements reflected the large intra- and interindividual variability of oxHb and tHb in the brain. The absolute values obtained by reNIRS for tHb (6.3 +/- 1.7 mg/ml), oxHb (3.7 +/- 1.1 mg/ml), and SO2 (61 +/- 5%) matched expected values. In contrast, measurements of oxCyt aa3 were unstable and results unreliable. reNIRS reliably detected cerebral ischemia, verified by a reduction of rCBF to 11% of baseline. tHb dropped to 74 +/- 7% of baseline (P<0.001), reflecting ischemic microvascular vasoconstriction. oxHb and SO2 dropped to expected near-zero values (2 +/- 4 and 3 +/- 5% of baseline, respectively; P<0.001). We conclude that reNIRS provides reliable and reproducible absolute values for brain tissue tHb, oxHb, and SO2 in small rodents. Determination of physiological values requires measurements at multiple locations, while cerebral ischemia is reliably detected by continuous recordings at a single location.
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PMID:Measurement of absolute values of hemoglobin oxygenation in the brain of small rodents by near infrared reflection spectrophotometry. 1185 62

We investigated the value of brain oxygen partial pressure (P(br)O(2)) with respect to predicting cerebral energetic failure in a rabbit model of global cerebral ischemia and hypoxia. Local cortical blood flow (l(co)CBF), P(br)O(2), extracellular lactate, pyruvate, and glutamate concentrations, as well as microvascular hemoglobin saturation (S(mv)O(2)), cytochrome oxidase redox level (Cyt a+a(3) oxidation), and brain electrical activity, were assessed during variable degrees of cerebral ischemia and hypoxia, induced by cisternal infusion of artificial cerebrospinal fluid or an admixture of nitrous oxide to inspiratory gas in 10 animals each. Arteriovenous difference in oxygen content, cerebral metabolic rate for oxygen, and oxygen extraction were derived from multimodal data. P(br)O(2), S(mv)O(2), and Cyt a+a(3) oxidation were closely related to cerebral blood flow and indices of oxidative metabolism. P(br)O(2) </=8 mm Hg corresponded to l(co)CBF </=15 mL. 100 g(-1). min(-1), S(mv)O(2) </=9%, Cyt a+a(3) oxidation </=20%, and progressive loss of brain electrical activity. Adequate tissue oxygenation was reflected by cerebral metabolic rate for oxygen >/=2.8 mL. 100 g(-1). min(-1), arteriovenous difference in oxygen content </=12.5 mL O(2). 100 mL(-1), and oxygen extraction </=60%. Meaningful interpretation of low P(br)O(2), especially with respect to definition of energetic thresholds, requires complementary information from simultaneous assessment of l(co)CBF and tissue oxygen extraction. IMPLICATIONS. The relationship between brain oxygen partial pressure and several variables of energy metabolism was investigated during variable degrees of cerebral ischemia and hypoxia in a rabbit model. Correct interpretation of individual brain oxygen partial pressure values, especially with respect to definition of energetic thresholds, requires complementary information from assessment of cerebral blood flow and tissue oxygen extraction.
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PMID:Does tissue oxygen-tension reliably reflect cerebral oxygen delivery and consumption? 1235 Dec 91

Rational intervention in infants with posthemorrhagic hydrocephalus (PHH) would be facilitated greatly by bedside measure of impaired cerebral perfusion, as there is substantial evidence that impaired perfusion and oxidative metabolism contribute to irreversible brain injury in hydrocephalus. Near-infrared spectroscopy (NIRS) measures changes in the cerebral concentration of oxygenated and deoxygenated hemoglobin and oxidized cytochrome oxidase at the bedside of infants continuously and noninvasively. The total hemoglobin and the hemoglobin difference signal are derived from the sum and difference, respectively, of oxygenated and deoxygenated hemoglobin. Changes in total hemoglobin reflect changes in cerebral blood volume; our previous work has shown that changes in hemoglobin difference signal reflect changes in cerebral blood flow. We hypothesized that cerebrospinal fluid (CSF) removal in infants with PHH would result in significant increases in cerebral perfusion, cerebral blood volume, and oxidative metabolism, as measured by NIRS. Continuous NIRS recordings were performed during CSF removal on 16 infants with PHH. There was a statistically significant increase in oxygenated hemoglobin (p < 0.001), total hemoglobin (p = 0.001), and hemoglobin difference signal (p = 0.006), but not oxidized cytochrome oxidase, accompanying CSF removal. There was no significant correlation between either the volume of CSF removed (in milliliters per kilogram body weight) or the opening pressure and the change in any of the measured or calculated NIRS signals. These findings demonstrate the pronounced effect of CSF removal on cerebral perfusion in infants with PHH. NIRS may be a useful technique to detect impending cerebral ischemia in such infants and thereby provide a means to guide the rational management of PHH.
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PMID:CSF removal in infantile posthemorrhagic hydrocephalus results in significant improvement in cerebral hemodynamics. 1473 52

Oxidative stress has been implicated in neuronal death caused by cerebral ischemia or some neurologic disorders. Chemical hypoxia (term defining the simulation by using respiratory inhibitors) chosen as in vitro ischemic model, was induced in primary cultures of rat cerebellar granule neurons by inhibitors of mitochondrial electron transport such as rotenone or paraquat (complex I), 3-nitropropionic acid (3-NPA, complex II), antimycin A (complex III), or sodium azide (complex IV). All compounds caused neuronal death determined by trypan blue staining and MTT-test. On the other hand, neurotoxicity of rotenone and paraquat but not of 3-NPA, antimycin or azide was significantly abolished by menadione (vitamin K3, 2-methyl-1,4-naphthoquinone). This neuroprotective effect of menadione was associated with a decrease of rotenone-induced free radical production.
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PMID:Menadione reduces rotenone-induced cell death in cerebellar granule neurons. 1537 39

Secondary brain damage plays a critical role in the outcome of patients with traumatic brain injury (TBI). The multiple mechanisms underlying secondary brain damage, including posttraumatic cerebral ischemia, glutamate excitotoxicity, oxidative stress, calcium overload and inflammation, are associated with increased mortality and morbidity after head injury. TBI is documented to have detrimental effects on mitochondria, such as alterations in glucose utilization and the depression of mitochondrial oxidative phosphorylation. Studies on mitochondrial metabolism have provided evidence for dysfunction of the cytochrome oxidase complex of the electron transport chain (complex IV) after TBI. A growing body of evidence indicates that cytochrome c oxidase is vital for mitochondrial oxidative phosphorylation. Therefore, this study aimed to detect the expression of cytochrome c oxidase (CO) mRNA in a rat weight-dropping trauma model and to clarify the differences between injured cortex (IC) and contralateral cortex (CC) after TBI. A total of forty-four rats were randomly assigned to 7 groups: control groups (n=4), sham-operated group (n=20), 6 h, 1 d, 3 d, 5 d and 7 d postinjury groups (n=4 for each group). The group consisted of sham-operated animals underwent parietal craniotomy without TBI. The rats in postinjury groups were subjected to TBI. The rats of control group were executed immediately without TBI or craniotomy after anesthesia. The brain-injured and sham-operated animals were killed on 6 h, 1 d, 3 d, 5 d and 7 d, respectively. Tissue sections from IC and CC were obtained and the expression of cytochrome c oxidase I, II, and III (CO I, II, III) mRNA, three mitochondrial encoded subunits of complex IV, were assessed by Real-time quantitative PCR. A reduction of CO I, II, and III mRNA expression was detected from IC and reduced to the lowest on 3 d. By contrast, the mRNA expression from CC suggested a slight elevation. The differences may indicate the degree of metabolic and physiologic dysfunction. Our results will better define the roles of gene expression and metabolic function in long-term prognosis and outcome after TBI. With a considerable understanding of post-injury mitochondrial dysfunction, therapeutic interventions targeted to the mitochondria may prevent secondary brain damage that leads to long-term cell death and neurobehavioral disability.
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PMID:Quantitative detection of the expression of mitochondrial cytochrome c oxidase subunits mRNA in the cerebral cortex after experimental traumatic brain injury. 1906 73

The effect of ageing and the relationships between the catalytic properties of enzymes linked to Krebs' cycle, electron transfer chain, glutamate and aminoacid metabolism of cerebral cortex, a functional area very sensitive to both age and ischemia, were studied on mitochondria of adult and aged rats, after complete ischemia of 15 minutes duration. The maximum rate (Vmax) of the following enzyme activities: citrate synthase, malate dehydrogenase, succinate dehydrogenase for Krebs' cycle; NADH-cytochrome c reductase as total (integrated activity of Complex I-III), rotenone sensitive (Complex I) and cytochrome oxidase (Complex IV) for electron transfer chain; glutamate dehydrogenase, glutamate-oxaloacetate-and glutamate-pyruvate transaminases for glutamate metabolism were assayed in non-synaptic, perikaryal mitochondria and in two populations of intra-synaptic mitochondria, i.e., the light and heavy mitochondrial fraction. The results indicate that in normal, steady-state cerebral cortex, the value of the same enzyme activity markedly differs according (a) to the different populations of mitochondria, i.e., non-synaptic or intra-synaptic light and heavy, (b) and respect to ageing. After 15 min of complete ischemia, the enzyme activities of mitochondria located near the nucleus (perikaryal mitochondria) and in synaptic structures (intra-synaptic mitochondria) of the cerebral tissue were substantially modified by ischemia. Non-synaptic mitochondria seem to be more affected by ischemia in adult and particularly in aged animals than the intra-synaptic light and heavy mitochondria. The observed modifications in enzyme activities reflect the metabolic state of the tissue at each specific experimental condition, as shown by comparative evaluation with respect to the content of energy-linked metabolites and substrates. The derangements in enzyme activities due to ischemia is greater in aged than in adult animals and especially the non-synaptic and the intra-synaptic light mitochondria seems to be more affected in aged animals. These data allow the hypothesis that the observed modifications of catalytic activities in non-synaptic and intra-synaptic mitochondrial enzyme systems linked to energy metabolism, amino acids and glutamate metabolism are primary responsible for the physiopathological responses of cerebral tissue to complete cerebral ischemia for 15 min duration during ageing.
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PMID:Effect of ageing and ischemia on enzymatic activities linked to Krebs' cycle, electron transfer chain, glutamate and aminoacids metabolism of free and intrasynaptic mitochondria of cerebral cortex. 1949 70


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