Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.
 ...
PMID:Seizure-associated pulmonary edema and cerebral oxygenation in the rat. 355 25

To investigate how mitochondrial function was affected in leukotoxin (Lx)-,9,10-epoxy-12-octadecenoate-induced lung injury, lung mitochondria were extracted from isolated perfused rat lung with or without Lx-induced edematous injury. In the lung treated with 30 mumol of Lx, the mitochondrial respiration rate in states 3 and 4 significantly decreased (without mitochondrial uncoupling) concomitantly with increased release of lactate dehydrogenase (LDH), a parameter for cellular damage, into the perfusate and decreased ATP content in the lung tissue compared with those of untreated lung. Moreover, 30 mumol of Lx resulted in significant inhibition of cytochrome-c oxidase activity (vs. vehicle control). In contrast, lower doses of Lx (10 mumol) caused lung edema and cellular damage without evidence for mitochondrial dysfunction. We also examined cellular and mitochondrial damage in hydrostatic lung edema. Such edema showed neither suppressed mitochondrial respiration nor elevated LDH activity in perfusate, although lung wet weight increased as much as it did after 30 mumol Lx treatment. Our results suggest that the ex vivo mitochondrial dysfunction is one of the secondary (vs. initial augmented permeability) but specific manifestations of toxicity of Lx, and together with the previous reports, the ex vivo damaging effect of Lx against mitochondria may be ascribed not to its direct action on mitochondria but to Lx-derived cellular mechanism(s).
 ...
PMID:Leukotoxin, 9,10-epoxy-12-octadecenoate inhibits mitochondrial respiration of isolated perfused rat lung. 757 65

Hydrogen sulphide (H2S) is the primary chemical hazard in natural gas production in 'sour' gas fields. It is also a hazard in sewage treatment and manure-containment operations, construction in wetlands, pelt processing, certain types of pulp and paper production, and any situation in which organic material decays or inorganic sulphides exist under reducing conditions. H2S dissociates into free sulphide in the circulation. Sulphide binds to many macromolecules, among them cytochrome oxidase. Although this is undoubtedly an important mechanism of toxicity due to H2S, there may be others H2S provides little opportunity for escape at high concentrations because of the olfactory paralysis it causes, the steep exposure-response relationships, and the characteristically sudden loss of consciousness it can cause which is colloquially termed 'knockdown.' Other effects may include mucosal irritation, which is associated at lower concentrations with a keratoconjunctivitis called 'gas eye' and at higher concentrations with risk of pulmonary oedema. Chronic central nervous system sequelae may possibly follow repeated knockdowns: this is controversial and the primary effects of H2S may be confounded by anoxia or head trauma. Treatment is currently empirical, with a combination of nitrite and hyperbaric oxygen preferred. The treatment regimen is not ideal and carries some risk.
 ...
PMID:Hydrogen sulphide. 891 53

To study the mechanism of pulmonary edema after seawater drowning (PE-SWD), the indexes of blood-gas and acid-base in rabbits artery blood were measured by the blood-gas analyser. The activity of Na(+)-K(+)-ATPase, cytochrome oxidase(CYTO) and alkaline phospharase(ALP) in the lungs were measured and analysed by computer image system. C-fos mRNA and Fos protein in the lungs were respectively determined by situ hybrioization and immunohisto chemical techniques. The distribution of phospholipid and Ca2+ of rabbits lungs was quantitatively analysed by ultrastructural location method. The results showed that, five parameters of PaO2, oxygen saturation(SaO2), pH, actual bicarbonite(AB) and base excess(BE) and the activity of Na(+)-K(+)-ATPase and CYTO decreased remarkably in PE-SWD. Both c-fos mRNA and Fos protein expression in pulmonary epithelial cells in PE-SWD were significantly elevated compared with the normal controls(P < 0.01). The phospholipids products in the pulmonary alveolar type II epithelial cells were decreased, however, the Ca2+ precipitate pellets inside the lung capillary endothelial cells and the pulmonary alveolar type I and II epithelial cells increased obviously. The arthors suggest that the injuny action of the seawater, hypoxia and metabolic acidosis may be the mian three mechanisms of the pulmonary edema induced seawater drowning. The lowering activity of Na(+)-K(+)-ATPase and CYTO in the lungs and calcium overload in the cells are not only evil consequence resulted from above three factors, but also the importent causes leading to the worse of PE-SWD. The transmiting line of Ca(2+)-fos may be also a key link to bring about the worse of PE-SWD.
 ...
PMID:[Study on the mechanism of pulmonary edema after seawater drowning in rabbit]. 1255 79

Sojourns to high altitude have become common for recreation and adventure purposes. In most individuals, gradual ascent to a high altitude leads to a series of adaptive changes in the body, termed as acclimatization. These include changes in the respiratory, cardiovascular, hematologic systems and cellular adaptations that enhance oxygen delivery to the tissues and augment oxygen uptake. Thus there is an increase in pulmonary ventilation, increase in diffusing capacity in the lung, an increase in the cardiac output and increase in the red blood cell count due to an increase in erythropoietin secretion by the kidney, all of which enhance oxygen delivery to the cells. Cellular changes like increase in the number of mitochondria and augmentation of cytochrome oxidase systems take months or years to develop. Too rapid an ascent or inability to acclimatize leads to high-altitude illnesses. These include acute mountain sickness (AMS), high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE). Acute mountain sickness is self limiting if recognized early. Both HACE and HAPE are life threatening and need to be treated aggressively. The key to treatment of these illnesses is early recognition; administration of supplemental oxygen; and descent if required. Drugs like acetazolamide, dexamethasone, nifedipine may be administered as recommended.
 ...
PMID:High-altitude medicine. 2080 61

Hydrogen sulfide (H2S) is a hazard primarily in the oil and gas industry, agriculture, sewage and animal waste handling, construction (asphalt operations and disturbing marshy terrain), and other settings where organic material decomposes under reducing conditions, and in geothermal operations. It is an insoluble gas, heavier than air, with a very low odor threshold and high toxicity, driven by concentration more than duration of exposure. Toxicity presents in a unique, reliable, and characteristic toxidrome consisting, in ascending order of exposure, of mucosal irritation, especially of the eye ("gas eye"), olfactory paralysis (not to be confused with olfactory fatigue), sudden but reversible loss of consciousness ("knockdown"), pulmonary edema (with an unusually favorable prognosis), and death (probably with apnea contributing). The risk of chronic neurcognitive changes is controversial, with the best evidence at high exposure levels and after knockdowns, which are frequently accompanied by head injury or oxygen deprivation. Treatment cannot be initiated promptly in the prehospital phase, and currently rests primarily on supportive care, hyperbaric oxygen, and nitrite administration. The mechanism of action for sublethal neurotoxicity and knockdown is clearly not inhibition of cytochrome oxidase c, as generally assumed, although this may play a role in overwhelming exposures. High levels of endogenous sulfide are found in the brain, presumably relating to the function of hydrogen sulfide as a gaseous neurotransmitter and immunomodulator. Prevention requires control of exposure and rigorous training to stop doomed rescue attempts attempted without self-contained breathing apparatus, especially in confined spaces, and in sudden release in the oil and gas sector, which result in multiple avoidable deaths.
...
PMID:Hydrogen sulfide intoxication. 2656 86

Bovine pulmonary artery endothelial cells (BPAEC) respond in a dose-dependent manner to millimolar (0-10) levels of sodium sulfide (NaHS). No measurable increase in caspase-3 activity and no change in the extent of autophagy (or mitophagy) were observed in BPAEC. However, lactate dehydrogenase levels increased in the BPAEC exposed NaHS, which indicated necrotic cell death. In the case of galactose-conditioned BPAEC, the toxicity of NaHS was increased by 30% compared to that observed in BPAEC maintained in the regular glucose-containing culture medium, which indicated a link between mitochondrial oxidative phosphorylation and the mechanism of toxicant action. This is consistent with the widely held view that cytochrome c oxidase (complex IV of the mitochondrial electron-transport system) is the principal molecular target involved in the acute toxicity of "sulfide" (H2S/HS-). In support of this view, elevated NO (which can reverse cytochrome c oxidase inhibition) ameliorated the toxicity of NaHS and, conversely, suppression of endogenous NO production exacerbated the observed toxicity. Respirometric measurements showed the BPAEC to possess a robust sulfide oxidizing system, which was able to out-compete cytochrome c oxidase for available H2S/HS- at micromolar concentrations. This detoxification system has previously been reported by other groups in several cell types, but notably, not neurons. The findings appear to provide some insight into the question of why human survivors of H2S inhalation frequently present at the clinic with respiratory insufficiency/pulmonary edema, while acutely poisoned laboratory animals tend to either succumb to cardiopulmonary paralysis or fully recover without any intervention.
 ...
PMID:Sulfide Toxicity and Its Modulation by Nitric Oxide in Bovine Pulmonary Artery Endothelial Cells. 2908 35