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)

The rat nasolabialis muscle is comprised of a mosaic of red, white, and intermediate muscle fiber types. Using computerized microdensitometry, cytochrome oxidase (COX) activity was quantitatively analyzed in each fiber type throughout the period of denervation and recovery in young adult (3-month) and middle-aged (15-month) male Sprague-Dawley rats. In animals of both age groups, the nasolabialis muscle on one side of the head was denervated by crushing the facial nerve. At specific days post crush (dpc) ranging from 2 days-2 months, animals were sacrificed and thick sections of normal and denervated muscles were incubated to demonstrate the activity of COX, a mitochondrial enzyme, which differentiates between the three fiber types. Enzyme activities in individual fibers were microdensitometrically analyzed using a digitizing image analyzer. Although a denervation-induced decreased followed by eventual recovery occurred in all fibers of each type, age-related differences were evident. For all types, younger fibers consistently showed decreased COX activity sooner than their older counterparts, and older fibers of all types consistently showed a greater decreased COX activity than the younger fibers. Denervation-induced de-differentiation of muscle fibers led to a more homogeneous population of fiber types in both age groups. Following recovery of function, the magnitude of the fiber enzyme activity change differed according to fiber type and to age, and was consistently smaller in older animals. The normal mosaic pattern of fiber type distribution and normal COX levels were restored 2 months after nerve lesion in both age groups.
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PMID:Age effects on cytochrome oxidase activities during denervation and recovery of three muscle fiber types. 165 12

Advancing age affects the ability of motor neurons to regrow axons after the facial nerve is crushed. In rats, it requires 14 days after injury for 3-month-old animals to resume normal whisker activity, compared to at least 19 days in 15-month-old animals. The present study examines central enzymatic responses of facial motor neurons to axotomy. During the postoperative period from 1 day through 8 weeks, alternate frozen sections of brain stem are histochemically reacted to demonstrate activities of acetylcholinesterase (AChE) or cytochrome oxidase (COX) and the reactions are quantified using computerized image analyzing densitometry. AChE activity is evaluated separately in perikaryal cytoplasm and neuropil, while COX is assayed in the facial nucleus as a whole. Coincident with the initiation of axon outgrowth the activities of these enzymes decrease in the neurons. For AChE the decrease is greater in the older animals; for COX the decrease is equivalent in both age groups. With regard to the perikaryal AChE and the neuropil AChE, the recovery patterns are different in the two locations. In the perikarya AChE activity begins to recover after 4 days in both age groups; however, AChE activity in the neuropil remains decreased until after functional recovery of whisker activity, when it recovers rapidly in the 3-month-old animals, but more gradually in the 15-month-old animals. In both age groups, COX activity gradually decreases in response to axotomy. In the 3-month-old animals it recovers rapidly following return of whisker activity, while in the 15-month animals COX activity is maintained at the decreased level through 28 days post-crush, before it begins its gradual recovery. The study demonstrates that age differences are most apparent after the reestablishment of functional connections. This age-related deficiency may be related to deficiencies in retrogradely transported signals arising from the reinnervated target or in the older neuron's ability to respond to such signals.
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PMID:The effects of age on enzyme activities in the rat facial nucleus following axotomy: acetylcholinesterase and cytochrome oxidase. 216 14

Previously, we have shown that potassium and magnesium (K-Mg, 20 mM each) cardioplegia ameliorated cytosolic calcium ([Ca2+]i) accumulation and was associated with enhanced functional recovery after surgically induced global ischemia in the aged heart. K-Mg cardioplegia was also shown to enhance cytosolic cytochrome oxidase I activity and mRNA levels, suggesting that enhanced functional recovery may involve the preservation of high-energy phosphates. To investigate this hypothesis, 31P nuclear magnetic resonance was used to measure serial alterations in phosphocreatine (PCr), inorganic phosphate, nucleoside triphosphate (NTP), intracellular free magnesium (Mgf), and intracellular pH (pHi) in Langendorff-perfused, aged (135 wk) rabbit hearts during preischemia, global ischemia (30 min), and reperfusion (30 min). K-Mg cardioplegia retarded PCr depletion (P < 0.05) and significantly enhanced NTP preservation (P < 0.05) during ischemia and reperfusion. K-Mg cardioplegia also attenuated the increase in Mgf during ischemia (P < 0.05). These results were correlated with amelioration of [Ca2+]i accumulation during ischemia and preservation of left ventricular function after reperfusion and suggest that optimal functional recovery from surgically induced ischemia is provided by K-Mg cardioplegia in the aged myocardium.
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PMID:Amelioration of ischemic calcium overload correlates with high-energy phosphates in senescent myocardium. 924 17

Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and the administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of 11 subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilateral to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans.
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PMID:Alleviation of brain injury-induced cerebral metabolic depression by amphetamine: a cytochrome oxidase histochemistry study. 1070 18

We investigated the role of nitric oxide (NO) in the mitochondrial derangement associated with the functional response to ischemia-reperfusion of hyperthyroid rat hearts. Mitochondria were isolated at 3000 g from hearts subjected to ischemia-reperfusion, with or without N(omega)-nitro-L-arginine (L-NNA, an NO synthase inhibitor). During reperfusion, hyperthyroid hearts displayed tachycardia and low functional recovery. Their mitochondria exhibited O(2) consumption similar to euthyroid controls, while H(2)O(2) production, hydroperoxide, protein-bound carbonyl and nitrotyrosine levels, and susceptibility to swelling were higher. L-NNA blocked the reperfusion tachycardic response and increased inotropic recovery in hyperthyroid hearts. L-NNA decreased mitochondrial H(2)O(2) production and oxidative damage, and increased respiration and tolerance to swelling. Such effects were higher in hyperthyroid preparations. These results confirm the role of mitochondria in ischemia-reperfusion damage, and strongly suggest that NO overproduction is involved in the high mitochondrial dysfunction and the low recovery of hyperthyroid hearts from ischemia-reperfusion. L-NNA also decreased protein content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000 g. This and previous results suggest that the above fraction contains, together with light mitochondria, damaged mitochondria coming from the heaviest fraction, which has the highest cytochrome oxidase activity and capacity to produce H(2)O(2). Therefore, we propose that the high mitochondrial susceptibility to swelling, favoring mitochondrial population purification from H(2)O(2)-overproducing mitochondria, limits hyperthyroid heart oxidative stress.
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PMID:Role of nitric oxide in the functional response to ischemia-reperfusion of heart mitochondria from hyperthyroid rats. 1533 54

Photobiomodulation by light in the red to near infrared range (630-1000 nm) using low energy lasers or light-emitting diode (LED) arrays has been shown to accelerate wound healing, improve recovery from ischemic injury in the heart and attenuate degeneration in the injured optic nerve. Recent evidence indicates that the therapeutic effects of red to near infrared light result, in part, from intracellular signaling mechanisms triggered by the interaction of NIR light with the mitochondrial photoacceptor molecule cytochrome c oxidase. We have demonstrated that NIR-LED photo-irradiation increases the production of cytochrome oxidase in cultured primary neurons and reverses the reduction of cytochrome oxidase activity produced by metabolic inhibitors. We have also shown that NIR-LED treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. Photobiomodulation improves wound healing in genetically diabetic mice by upregulating genes important in the promotion of wound healing. More recent studies have provided evidence for the therapeutic benefit of NIR-LED treatment in the survival and functional recovery of the retina and optic nerve in vivo after acute injury by the mitochondrial toxin, formic acid generated in the course of methanol intoxication. Gene discovery studies conducted using microarray technology documented a significant upregulation of gene expression in pathways involved in mitochondrial energy production and antioxidant cellular protection. These findings provide a link between the actions of red to near infrared light on mitochondrial oxidative metabolism in vitro and cell injury in vivo. Based on these findings and the strong evidence that mitochondrial dysfunction is involved in the pathogenesis of numerous diseases processes, we propose that NIR-LED photobiomodulation represents an innovative and non-invasive therapeutic approach for the treatment of tissue injury and disease processes in which mitochondrial dysfunction is postulated to play a role including diabetic retinopathy, age-related macular degeneration, Leber's hereditary optic neuropathy and Parkinson's disease.
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PMID:Mitochondrial signal transduction in accelerated wound and retinal healing by near-infrared light therapy. 1612 Apr 14

Myocardial injury is increased in the aged heart during ischemia and reperfusion. Aging decreases oxidative metabolism in interfibrillar mitochondria (IFM) located between the myofibrils. We asked whether reversal of aging defects in IFM before ischemia would decrease injury in the aged heart following ischemia and reperfusion. Treatment with acetylcarnitine (AcCN) increases the activity of cytochrome oxidase in the aged heart. Aged (24 months) and adult (6 months) Fischer 344 rats were treated with AcCN (300 mg/kg i.p. 3 h before excision of the heart) or served as controls. AcCN restored oxidative phosphorylation and the activity of complexes III and IV in IFM from aged hearts to rates present in adults. Isolated hearts underwent 25 min global ischemia and 30 min reperfusion without additional treatment. Contractile recovery during reperfusion improved in hearts from AcCN-treated aged rats compared to aged controls and were similar to adults in recovery. AcCN-treated aged hearts sustained less damage, indicated by decreased lactate dehydrogenase (LDH) release during reperfusion. AcCN treatment did not alter functional recovery or LDH release in adults. Restoration of mitochondrial function in the aged heart before ischemia was accompanied by enhanced contractile recovery and decreased tissue injury following ischemia and reperfusion.
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PMID:Reversal of mitochondrial defects before ischemia protects the aged heart. 1679 72

Mitochondrial dysfunction is a key pathologic event in cardiac ischemia-reperfusion (IR) injury, and protection of mitochondrial function is a potential mechanism underlying ischemic preconditioning (IPC). Acknowledging the role of nitric oxide (NO()) in IPC, it was hypothesized that mitochondrial protein S-nitrosation may be a cardioprotective mechanism. The reagent S-nitroso-2-mercaptopropionyl-glycine (SNO-MPG) was therefore developed to enhance mitochondrial S-nitrosation and elicit cardioprotection. Within cardiomyocytes, mitochondrial proteins were effectively S-nitrosated by SNO-MPG. Consistent with the recent discovery of mitochondrial complex I as an S-nitrosation target, SNO-MPG inhibited complex I activity and cardiomyocyte respiration. The latter effect was insensitive to the NO() scavenger c-PTIO, indicating no role for NO()-mediated complex IV inhibition. A cardioprotective role for reversible complex I inhibition has been proposed, and consistent with this SNO-MPG protected cardiomyocytes from simulated IR injury. Further supporting a cardioprotective role for endogenous mitochondrial S-nitrosothiols, patterns of protein S-nitrosation were similar in mitochondria isolated from Langendorff perfused hearts subjected to IPC, and mitochondria or cells treated with SNO-MPG. The functional recovery of perfused hearts from IR injury was also improved under conditions which stabilized endogenous S-nitrosothiols (i.e. dark), or by pre-ischemic administration of SNO-MPG. Mitochondria isolated from SNO-MPG-treated hearts at the end of ischemia exhibited improved Ca(2+) handling and lower ROS generation. Overall these data suggest that mitochondrial S-nitrosation and complex I inhibition constitute a protective signaling pathway that is amenable to pharmacologic augmentation.
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PMID:Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury. 1735 35

The nature of mitochondrial dysfunction in dopaminergic neurons in familial Parkinson's disease (PD) is unknown. We characterized the pathophenotypes of dopaminergic neuronal cells that were deficient in PINK1 or DJ-1, genes with mutations linked to familial PD. Both PINK1- and DJ-1-deficient dopaminergic neurons had the increased production of ROS, severe mitochondrial structural damages and complex I deficits. A striking decrease in complex IV activity was also prominent by the PINK1-deficiency. The complex I deficits were relatively PD-specific and were significantly improved by an antioxidant Trolox. These data suggest that mitochondrial deficits are severe in dopaminergic neurons in familial PD and antioxidant-mediated functional recovery is feasible.
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PMID:The antioxidant Trolox helps recovery from the familial Parkinson's disease-specific mitochondrial deficits caused by PINK1- and DJ-1-deficiency in dopaminergic neuronal cells. 2166 94

Induction of heat shock proteins (hsp) has been shown to protect cells from ischemia by providing transient tolerance against myocardial injury and improving postischemic functional recovery. Attenuation of ATP depletion and earlier restoration of ATP content on reperfusion are thought to play a role in this scenario. Hsp induction is accompanied by altered enzyme activity of the respiratory chain, the major generator of ATP under physiological conditions. This report addresses the question whether processing and final assembly of the active holoenzyme cytochrome c oxidase (CcO, complex IV), member of the respiratory chain, is compromised under hypoxic conditions unless protected by stress proteins. Special focus is laid on function of the enzyme's subunits and importance of cellular energy availability and maintenance.
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PMID:Heat shock protein expression and change of cytochrome c oxidase activity: presence of two phylogenic old systems to protect tissues in ischemia and reperfusion. 2179 94


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