Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to document the effect of age on alpha-glycerophosphate activity and pyridine nucleotide concentration in pancreatic islets isolated from rats. In order to do this, islets were isolated from pancreases of 2 and 12 month-old rats, and measurements made of alpha-glycerophosphate activity and of NAD+ and NADH, determinations were made following incubation at both basal (5.6 mM) and elevated glucose concentrations (28 mM). The results indicated that islet alpha-glycerophosphate dehydrogenase activity was decreased (P less than 0.001) by approximately 50% in the older rats. This was associated with an increase in mean (+/- SEM) basal NADH content (pmol/microgram DNA) in 12 month-old (4.48 +/- 0.31) as compared to 2 month-old rats (2.73 +/- 0.49). Although mean (+/- SEM) basal NAD+ levels (pmol/microgram DNA) were the same in 2 and 12 month-old rats (29.4 +/- 2.5 and 30.8 +/- 2.8, respectively), NAD+ content following incubation at elevated levels of glucose declined (absolutely and relatively) to a significantly greater degree in the younger rats. The incremental rise in islet NADH concentration following incubation at the elevated glucose concentration was similar in the two groups, but the relative increase was only approximately half as great in islets from 12 month-old rats. These data indicate that the age-related decline in the activity of alpha-glycerophosphate dehydrogenase, the enzyme regulating the glycerophosphate shuttle system in 12 month-old rats, is associated with alterations in islet pyridine nucleotide composition.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evidence for age-related changes in pyridine nucleotide content of isolated rat islets. 305 68

In the present studies, we demonstrate in buffer-perfused isolated working guinea pig hearts that indometacin reduces coronary flow rate in a dose-dependent manner (max 56.7 +/- 5.5%, SEM, n = 6, of control at 5 x 10(-6) mol/l of indometacin, P less than 0.01), and that this leads to a development of heterogeneous patterns of myocardial ischemia (elevated myocardial levels of reduced pyridine nucleotide, NADH) and depressed cardiac work (64.7 +/- 11.7%, SEM, of control at 5 x 10(-6) mol/l of indometacin, P less than 0.05). The effect of indometacin on coronary flow rate and consequently on myocardial tissue oxygenation was completely prevented by the preferential 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) (1 x 10(-6) mol/l), or the sulfidopeptide leukotriene receptor antagonist FPL 55712 (2 x 10(-5) mol/l), indicating that the isolated working guinea pig heart, even when deprived of blood, is able to produce vasoactive sulfidopeptide leukotrienes at significant levels. At higher concentrations of indometacin (5 x 10(-5) mol/l, 1 x 10(-4) mol/l), coronary flow rate returned to initial levels while cardiac work became further depressed despite normoxic levels of NADH. These data support that indometacin also has a direct suppressive effect on the myocardium independent of its coronary vascular effect. This conclusion is supported by the observation that addition of sodium arachidonate (6 x 10(-5) mol/l) completely inhibited the vascular effect of indometacin, but not the depressive effect on the myocardium. The divalent cation ionophore A23187 (6 x 10(-6) mol/l) had a strong positive chronotropic effect on the heart and a biphasic effect on coronary flow rate. After a brief period of increased coronary flow rate, presumably due to coronary vasodilatation, the ionophore caused a sustained reduction in coronary flow, and this was accompanied by high myocardial levels of NADH fluorescence of characteristically heterogeneous pattern. This is presumably caused by vasoconstrictory effects of elevated levels of intracellular Ca2+ of vascular smooth muscle, independent of stimulation of 5-lipoxygenase or cyclooxygenase pathways, since neither indometacin nor nordihydroguaiaretic acid modified the effect of A23187.
 ...
PMID:Modulation of coronary flow rate and cardiac contractility by the divalent cation ionophore A23187 and inhibitors of the cyclooxygenase and 5-lipoxygenase pathways: development of heterogeneous patterns of myocardial ischemia. 313 May 82

Activated macrophages inhibit replication of murine lymphoblastic leukemia L1210 cells without lysis. This inhibition of replication is associated with abnormalities of mitochondrial electron transport at the level of NADH dehydrogenase (NADH-DH) and succinate dehydrogenase (SDH). The mechanism of inhibition is unknown, although it has been demonstrated that as NADH-DH and SDH activity is lost, iron is released from cells. Because both NADH-DH and SDH contain numerous iron-sulfur clusters, damage to these structures may be one result of injury by activated macrophages. L1210 cells were labeled with 55Fe and co-cultivated with activated murine peritoneal macrophages (injured L1210 cells). At 48 h, injured L1210 cells had released 83 +/- 8% (mean +/- SEM of 55Fe activity into the media, compared with 25 +/- 4% release from control and 37 +/- 7% from nondividing mitomycin C-treated control cells. All cells were greater than 90% viable. These differences were also reflected in the iron content of the cells. Mitochondria were then separated by centrifugation after cell disruption and 55Fe activity was found to be similarly decreased in both mitochondrial and nonmitochondrial fractions of injured L1210 cells. To further characterize the changes in mitochondrial iron content, mitochondrial proteins from injured and control L1210 cells were separated by IEF and 55Fe activity of gel slices was determined. There was selective loss of 55Fe activity in the area of the gel corresponding to SDH and NADH-DH, suggesting that iron loss from iron-sulfur clusters may occur in L1210 cells injured by activated macrophages. Iron uptake into L1210 cells after removal from macrophages showed a rapid large influx of radioactive iron. L1210 cells in contact with macrophages appear to develop an iron-depleted state, which is dependent on the continued presence of macrophages.
 ...
PMID:Mitochondrial iron loss from leukemia cells injured by macrophages. A possible mechanism for electron transport chain defects. 339 40

This paper reviews recent work in the authors' laboratories that has led to new observations and thoughts concerning the mineralization of normal and rachitic chick growth cartilage. The proximal tibial growth cartilages of normal and rachitic chicks were rapidly frozen and prepared for SEM and biochemical studies. Using a scanning microfluorimetric technique we showed that at the mineralization front of normal and rachitic cartilage there is an abrupt change in chondrocyte metabolism. Thus cells in this region exhibited an increase in NADH and oxidative metabolism. In rickets, there was a decrease in the reduced pyridine nucleotide content of each of the zones. The reversal in chondrocyte metabolism was not due to low oxygen tension. SEM observations indicated that this region of cartilage was well supplied with vascular channels; moreover, mineral was first seen deposited in matrix in close proximity to the blood supply. Indeed these vascular channels appeared to be a basic architectural feature of normal cartilage, although disorganized in the rachitic state. The morphological studies also showed that gaps existed in the continuity of the mineral phase in normal cartilage. Although the rachitic cartilage does mineralize, discontinuities in the mineral distribution are much more severe, with the general failure of fusion of adjacent mineral clusters. These structures would serve as pathways for transport of nutritional factors and gases to chondrocytes that are distant from the vascular channels. Observation of hypertrophic cells reinforced the view that some osteoblasts represented a terminal stage in the maturation of chondrocytes.
 ...
PMID:Mineralization of normal and rachitic chick growth cartilage: vascular canals, cartilage calcification and osteogenesis. 361 60

The influence of high-intensity bicycle exercise on the redox level and lactate accumulation in skeletal muscle (m. quadriceps femoris) of man has been investigated. Six subjects exercised to exhaustion at a load corresponding to 100% VO2max. Muscle content of NADH, determined by the bioluminescence technique, increased from (means +/- SEM) 0.089 +/- 0.007 mmol/kg dry wt. at rest to 0.190 +/- 0.031 after 2 min of exercise (P less than 0.05) and to 0.213 +/- 0.021 at exhaustion (P less than 0.05). Values after 2 min exercise and at exhaustion were not statistically different (P greater than 0.05). Muscle lactate was increased 13-fold after 2 min of exercise and 22-fold at exhaustion as compared to the resting value. After 10 min recovery NADH was restored back to the pre-exercise level whereas muscle lactate was still elevated. The increase of muscle NADH during exercise is in contrast to earlier studies on isolated animal muscles, where an oxidation of NADH was observed during contractions. The difference might be due to the experimental model (isolated muscle vs. in vivo) or to the analytical method (qualitative data by reflectance fluorimetri from the surface of intact muscle vs. quantitative data from muscle extracts). Calculations of the cytosolic NADH concentration from the lactate dehydrogenase equilibrium show that 95% or more of the NADH is confined to the mitochondrial compartment. The observed increase of muscle NADH therefore imply that the redox potential of the mitochondria is decreased during intense exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:NADH in human skeletal muscle during short-term intense exercise. 398 70

(1) Biopsies from the gastrocnemius muscle of patients with Duchenne dystrophy were partitioned into a myofibrillar plus nuclear fraction, a mitochondrial fraction and a supernatant fraction. The fractions were assayed for mitochondrial enzymes and protein, in order to obtain information about the integrity of mitochondrial structure and function. Muscles from boys and adults without neuromuscular disease were treated likewise. (2) In adults, muscle possesses a significantly higher specific activity (on protein basis) of monoamine oxidase and rotenone-insenitive NADH-cytochrome c reductase (RINCR) than in boys. In childhood, monoamine oxidase activity increases with age. At the age of 5 yr, the specific activity is 50% of the adult value. RINCR activity is constant in childhood. With adolescence it increases from 20 +/- 2 (SEM) to 35 +/- 6 mumoles cytochrome c reduced per min per g protein, and it remains at this level. Palmitoyl-CoA synthetase activity remains constant with age. (3) In Duchenne dystrophy the extractable protein content from muscle is decreased to 75%. The specific activities of the matrix enzymes propionyl-CoA carboxylase and glutamate dehydrogenase are 1.8 and 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased. Of the outer membrane enzymes RINCR is 2.0 times increased, while palmitoyl-CoA synthetase is not changed in acitivity. In Duchenne dystrophy monoamine oxidase activity also increases with age. In part this may be due to mitochondria from adipose tissue and macrophages, which are increasingly present in older patients. The specific activities of enzymes with a predominant cytosolic localisation, creatine kinase and adenylate kinase, are increased by a factor of 1.5 and 1.7. (4) The subcellular distribution of the studied enzymes in human skeletal muscle was found to be similar as in animal studies. In mitochondrial fractions from Duchenne patients the recoveries of the following enzymes are decreased: glutamate dehydrogenase (from 25 to 9%), creatine kinase (1.1-0.66%), adenylate kinase (0.44-0.22%), hexokinase (7.1-2.7%), monoamine oxidase (36-21%), RINCR (30-17%), and palmitoyl-CoA synthetase (40-21%). The recoveries of last 3 mitochondrial outer membrane enzymes in the supernatant fractions are correspondingly increased. These results indicate an increased fragility of the mitochondrial membranes in dystrophic muscles. (5) The reported changes are clearly evident in a one-year-old patient, which indicates that the mitochondria are involved early in the disease process.
 ...
PMID:Early changes of muscle mitochondria in Duchenne dystrophy. Partition and activity of mitochondrial enzymes in fractionated muscle of unaffected boys and adults and patients. 624 85

The activities of three enzymes--two mitochondrial and one microsomal--were measured in isolated islets of Langerhans from 2-month-old and 12-month-old rats. Mitochondrial glycerophosphate dehydrogenase activity (expressed as nanomoles of iodonitrotetrazolium reduced per minute per milligram of protein), decreased (P less than 0.01) from a mean (+/- SEM) of 73.2 +/- 11.2 (2-month-old) to 34.7 +/- 5.9 (12-month-old). In contrast, activities of neither mitochondrial monoamine oxidase nor microsomal NADH cytochrome-c reductase changed with age. These results demonstrate that the activity of the glycerophosphate shuttle decreases as rats grow older, and it raises the possibility that the consequent difficulty in regenerating cytosolic NAD+ may play a role in the insulin secretory defect associated with aging.
 ...
PMID:Evidence of an age-related decline in mitochondrial glycerophosphate dehydrogenase activity of isolated rat islets. 635 35

This study examined the effect of an aldose reductase inhibitor (Sorbinil, CP 45634, Pfizer, Sandwich, Kent, United Kingdom) on the metabolite profile of the lens during the first week after induction of diabetes with alloxan. The lens content of sorbitol, fructose, glycerol 3-phosphate, and glucose 6-phosphate was, respectively, 0.33 +/- 0.03, 0.55 +/- 0.05, 0.10 +/- 0.01, and 0.074 +/- 0.006 mumol/g (means +/- SEM) in the control group rising to 12.2 +/- 0.52, 3.20 +/- 0.10, 0.76 +/- 0.10, and 0.200 +/- 0.009 in lenses from alloxan-diabetic rats. Sorbinil treatment (40 mg/kg) decreased the lens content of sorbitol to 0.60 +/- 0.06, fructose to 0.85 +/- 0.08, and glycerol 3-phosphate to 0.36 +/- 0.03 mumol/g; glucose 6-phosphate remained unchanged. Significantly, the lens content of glutathione was decreased to 60% of the normal value in the diabetic group, but was sustained at normal levels with Sorbinil treatment. The ATP content of the lens was not altered by diabetes or Sorbinil treatment at this time interval. Sorbinil has no significant effect on the above metabolites in the normal rat lens. The effect of Sorbinil in restoring normal levels of glutathione and glycerol 3-phosphate may be a potentially important facet of the action of this drug. The interlocking of metabolic pathways by the redox state of NAD+/NADH and NADP+/NADPH, their derangement in diabetes, and the wider effects of Sorbinil on the network of reactions in the lens are discussed.
 ...
PMID:The effect of an aldose reductase inhibitor (Sorbinil) on the level of metabolites in lenses of diabetic rats. 640 81

Serum bile acid concentrations have been shown to be a predictive indicator of hepatobiliary disease in persons. However, there has been only limited use of bile acid values in the clinical diagnosis of hepatobiliary disease in the dog and cat because of technical difficulties associated with many bile acid assays. A rapid enzymatic method previously developed for the quantitation of 3-hydroxy bile acids in persons has been adapted for use in the dog and cat. Nonsulfated 3-hydroxy bile acids are converted to 3-oxo bile acids by 3 alpha-hydroxysteroid dehydrogenase and reduction of NAD+ to NADH. In a coupled diaphorase catalyzed reaction, H+ is transferred to nitrotetrazolium blue to produce a diformazan dye, which is measured spectrophotometrically at 540 nm. Nonspecific interfering dehydrogenase activities present in the dog and the cat serums were inhibited by heating the serum to 60 C for 30 minutes or by the addition of sodium pyruvate. Standard curves prepared from various serum sodium taurocholate concentrations in dogs and cats are linear to 250 mumol/L. The assay is sensitive for the detection of bile acid concentrations as low as 2.5 mumol/L in sera from dogs and cats. In validation studies quantitative recovery of known concentrations of 7 primary and secondary, conjugated and unconjugated, 3-hydroxy bile acids from pooled canine serum was 95.3 +/- 7.9% (mean +/- SEM) and that from pooled feline serum was 101.4 +/- 8.2%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Direct spectrometric determination of serum bile acids in the dog and cat. 649 3

The effects of different levels of arterial blood oxygen content (CaO2) on brain tissue adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) were studied during cerebral hypoxia in normothermic and hypothermic male Wistar rats with unilateral carotid ligation. Animals were exposed to hypoxia (PaO2 19--26 torr) for 25 min, and brain tissue metabolite values measured microfluorometrically were compared with those of normothermic normoxic controls. CaO2 was 4.0 +/- 0.2 ml/dl (mean +/- SEM) at PaO2 26 torr in normothermic animals. CaO2 was increased to 8.2 +/- 0.3 ml/dl at PaO2 26 torr by means of bicarbonate infusion producing a leftward shift of the oxyhemoglobin-dissociation curve in one normothermic hypoxic group. In all normothermic hypoxic groups ATP and PCr decreased and lactate and NADH increased significantly compared with control values. There was no significant difference in brain tissue metabolite values among these groups despite an increase in CaO2 by twofold in one group. Hypothermia (32 C) resulted in CaO2 8.4 +/- 0.2 ml/dl at PaO2 26 torr. This was decreased to 4.0 +/- 0.2 ml/dl by decreasing PaO2 to 19 torr in another group at the same temperature. ATP and PCr were well preserved in both groups despite the difference in CaO2s. Although the lactate and NADH levels were increased in the hypothermic group with CaO2 4.0 +/- 0.2 ml/dl, they were significantly lower than those values in normothermic hypoxic groups. These results indicate that the increase in CaO2 produced by hypothermia is not a major determinant in hypothermic protection during cerebral hypoxia.
 ...
PMID:Effect of high vs. low arterial blood oxygen content on cerebral energy metabolite levels during hypoxia with normothermia and hypothermia in the rat. 676 65


<< Previous 1 2 3 4 5 Next >>