Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ca(2+)-independent form of nitric oxide synthase was induced in rat neonatal astrocytes in primary culture by incubation with lipopolysaccharide (1 microgram/ml) plus interferon-gamma (100 U/ml), and the activities of the mitochondrial respiratory chain components were assessed. Incubation for 18 h produced 25% inhibition of cytochrome c oxidase activity. NADH-ubiquinone-1 reductase (complex I) and succinate-cytochrome c reductase (complex II-III) activities were not affected. Prolonged incubation for 36 h gave rise to a 56% reduction of cytochrome c oxidase activity and a 35% reduction in succinate-cytochrome c reductase activity, but NADH-ubiquinone-1 reductase activity was unchanged. Citrate synthase activity was not affected by any of these conditions. The inhibition of the activities of these mitochondrial respiratory chain complexes was prevented by incubation in the presence of the specific nitric oxide synthase inhibitor NG-monomethyl-L-arginine. The lipopolysaccharide/interferon-gamma treatment of the astrocytes produced an increase in glycolysis and lactate formation. These results suggest that inhibition of the mitochondrial respiratory chain after induction of astrocytic nitric oxide synthase may represent a mechanism for nitric oxide-mediated neurotoxicity.
 ...
PMID:Nitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytes. 751 65

The effect of the neurotoxic nitric oxide derivative, the peroxynitrite anion (ONOO-), on the activity of the mitochondrial respiratory chain complexes in cultured neurones and astrocytes was studied. A single exposure of the neurones to ONOO- (initial concentrations of 0.01-2.0 mM) caused, after a subsequent 24-h incubation, a dose-dependent decrease in succinate-cytochrome c reductase (60% at 0.5 mM) and in cytochrome c oxidase (52% at 0.5 mM) activities. NADH-ubiquinone-1 reductase was unaffected. In astrocytes, the activity of the mitochondrial complexes was not affected up to 2 mM ONOO-. Citrate synthase was unaffected in both cell types under all conditions studied. However, lactate dehydrogenase activity released to the culture medium was increased by ONOO- in a dose-dependent manner (40% at 0.5 mM ONOO-) from the neurones but not from the astrocytes. Neuronal glutathione concentration decreased by 39% at 0.1 mM ONOO-, but astrocytic glutathione was not affected up to 2 mM ONOO-. In isolated brain mitochondria, only succinate-cytochrome c reductase activity was affected (22% decrease at 1 mM ONOO-). We conclude that the acute exposure of ONOO- selectively damages neurones, whereas astrocytes remain unaffected. Intracellular glutathione appears to be an important factor for ameliorating ONOO(-)-mediated mitochondrial damage. This study supports the hypothesis that the neurotoxicity of nitric oxide is mediated through mitochondrial dysfunction.
 ...
PMID:Effect of peroxynitrite on the mitochondrial respiratory chain: differential susceptibility of neurones and astrocytes in primary culture. 772 84

Adaptative changes in skeletal muscle following surface electrical stimulation (SES) were investigated in rhesus monkeys. SES was performed on the triceps brachialis muscle (TB) according to an intermittent pattern. The procedure was carried out for 3 wk, using a current with a medium frequency of 60 Hz normally observed in fast motor axons. The histochemical assays performed on biopsies taken from proximal and distal parts of the TB muscle, before and after the SES program, showed that the distribution of fibers typed by ATPase was unaffected. On the other hand, SES led to an overall increase in the mean fiber cross-sectional area (FCSA); P < 0.01 (+13.7%, NS, in proximal portion, vs +31%, P < 0.01 in distal portion). This increase in size occurred in all fiber types. SES was shown to induce an overall increase in capillary to fiber ratio (C/F; +11.06%, NS, in proximal portion, vs +25.93%, P < 0.05 in distal portion). The number of capillaries surrounding fiber Type II (CAFII) was significantly increased by SES (P < 0.05): +3.21%, NS, in proximal portion, versus +21.47%, P < 0.05 in distal portion. Moreover, the number of capillaries surrounding fiber Type I (CAFI) was statistically unaffected by SES. These results suggest that a stimulation of capillary growth may occur following SES-training. Citrate synthase activity was significantly increased after SES. This enhancement in oxidative potential was shown to occur in all fiber types (NADH-diaphorase staining).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of surface electrostimulation on the structure and metabolic properties in monkey skeletal muscle. 845 51

Mitochondrial biogenesis was studied during differentiation of two immortalized cell lines (C2C12, 3T3) with enzyme measurements, Northern blots, and quantitative ultrastructure. Citrate synthase, isocitrate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase (nuclear encoded, mitochondrial matrix location) showed linear, four- to sixfold increases in enzymatic activity in C2C12 cells but increased exponentially in 3T3 cells. Cytochrome oxidase and NADH dehydrogenase (nuclear and mitochondrial encoded, cristae location) increased to a lesser extent and with a pattern dissimilar to the first group. Northern blots and activity of succinate dehydrogenase (cristae location but entirely nuclear encoded) suggested the groupings were based on location of the genes rather than the mature enzyme. However, quantitative electron microscopy and comparisons with adult tissue suggested that mitochondrial ultrastructure can influence the change in cristae enzymes. Cristae surface area per unit mitochondrial volume and per unit cell volume increased much less than did cristae enzymes. Available space on the inner membrane may become limiting and account for some aspects of the pattern of change in electron transport enzymes during differentiation.
 ...
PMID:Mitochondrial biogenesis during cellular differentiation. 914 61

In spite of opposing changes in rates of adenosine triphosphate turnover, hypertrophy and atrophy of the heart are accompanied by the same changes in gene expression, resembling a fetal genotype. Fetal hearts are characterized by increased ischemia tolerance. We assessed respiratory capacity of mitochondrial subpopulations from unloaded and pressure-overloaded hearts before and after 15 minutes of normothermic ischemia. Unloading was achieved by heterotopic rat heart transplantation and overloading by aortic banding. Respiratory chain gene expression (NADH dehydrogenase, cytochrome c oxidase [COX]) were analyzed by reverse transcriptase-polymerase chain reaction. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated by differential centrifugation. Citrate synthase was used as mitochondrial marker enzyme. Adenosine diphosphate-stimulated oxygen consumption (state 3) was measured with a Clark-type electrode. Unloading resulted in atrophy, overloading in hypertrophy. State 3 was reduced in atrophied hearts both in SSM and IFM (SSM: 204 +/- 79 vs 804 +/- 147 natoms oxygen min(-1) mL(-1), P < .001; IFM: 468 +/- 158 vs 1141 +/- 296 natoms oxygen min(-1) mL(-1), P < .05), but was unchanged in hypertrophied hearts. NADH dehydrogenase and COX expression was also decreased with atrophy and was unchanged with hypertrophy. Ischemia caused decreased recovery of citrate synthase in isolates of SSM (P < .05) but not of IFM. State 3 in control hearts was reduced in IFM (-41%, P < .01) and SSM (-19%, not significant). This ischemia-induced decrease was less pronounced in SSM (-2%) and IFM (-22%) of atrophied and IFM (-23%) of hypertrophied hearts. Subsarcolemmal mitochondria of hypertrophied hearts displayed the greatest ischemia-induced decrease of state 3 (-32%, P < .05). In conclusion, (1) long-term changes in workload differentially affect maximal respiratory capacity and ischemia tolerance of isolated mitochondria. The changes are not parallel to the changes in energy requirements. (2) Mitochondria of atrophied hearts appear to be more resistant against ischemia than controls.
 ...
PMID:Differential changes in respiratory capacity and ischemia tolerance of isolated mitochondria from atrophied and hypertrophied hearts. 1683 47