Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary protein deficiency is known to modify the response to the pharmacotoxicological activities of drugs and foreign compounds, due in part to altered rates of metabolism. Prediction of whether in vivo susceptibilities to foreign compounds are increased or decreased in protein deficient animals has been said to be related to the relative toxicites of the metabolic products. We have shown that weanling rats fed semipurified casein diets for 15 days show a 75% depression of hepatic microsomal mixed function oxidase activities. About one-fourth of this decrease is due to a retardation of the normal rate of liver cell proliferation and less microsomal protein; the remaining three-fourths is due to a reduction of the specific enzyme activity. This latter decrease is closely correlated with similar decreases in cytochrome P-450 and cytochrome c reductase activities and cytochrome P-450 contents. Although protein deficiency affects the relative contents of phosphatidylcholine and cytochrome P-450, this does not result in modifications of the Km for metabolism, as is seen with phenobarbital administration in the various dietary groups. The depression of mixed function oxidase enzyme activities caused by feeding the protein deficient diet for 15 days can be restored to normal by feeding the 20% casein diets for an additional 30 days in the case of aniline hydroxylase but only partially in the case of ethylmorphine N-demethylase. The complexities of determining the role of metabolism as a modulator of protein deficiency effects on foreign compound toxicity are discussed.
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PMID:The effect of quantity and quality of dietary protein on drug metabolism. 97 91

Six different lipophilic (hydrophobic) organic cations, tetraethyl-, tetrapropyl, tetrabutyl-, tetrapentyl-, tetrahexyl-, and tetraheptylammonium bromide, depressed respiratory control in rat liver mitochondria. Evaluation of mitochondrial responses in terms of a quadratic equation in log P (an index of lipophilicity) indicated that the NADH dehydrogenase receptor site for inhibitor (diminution of control of glutamate, alpha-ketoglutarate, and beta-hydroxybutyrate respiration) was more lipophilic than receptor sites for flavin-linked substrates (reduction of control of succinate, choline and alpha-glycerophosphate respiration). The succinate dehydrogenase receptor site for inhibition by the tetraalkylammonium bromides was more hydrophillic (less lipophilic) than the choline or alpha-glycerophosphate dehydrogenase receptor sites. Depression of respiratory control may be a function of charge density and of lipophilicity at specific inner membranal sites and the susceptible site may differ for different respiratory substrates.
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PMID:Respiratory control depression by tetraalkylammonium bromides in rat liver mitochondria. 124 57

Steady-state levels of 12 S and 16 S mitochondrial (mt) rRNAs and four mRNAs (NADH dehydrogenase subunits 3 and 4/4L, cytochrome c oxidase subunit III, H(+)-ATPase subunits 6/6L) were estimated by hybridization of cellular RNA with cloned human mt DNA fragments during hypoxia of HeLa cells. When the partial pressure of oxygen (pO2) was shifted from 135 to 15 Torr, the level of all mRNAs coordinately decreased more than 95% in 48 h, while that of rRNAs remained virtually unchanged. mRNA levels recovered within 4-6 h of reexposure to normoxia. The depression was observed at pO2 less than 40 Torr, the physiological pO2 in peripheral tissues. During these transitions, the growth rate of HeLa cells and the copy number of mt DNA per cell remained unchanged. The degradation rate of mt mRNAs in the presence of cordycepin was not affected by pO2. In contrast to the in vivo results, the potential activity of transcription in isolated mitochondria assayed under optimum conditions was not affected by previous hypoxic exposure of the cells. These observations provide evidence for the existence of a new mechanism controlling mitochondrial gene transcription.
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PMID:Hypoxic depression of mitochondrial mRNA levels in HeLa cell. 170 27

Saline extracts of burn eschar (CEBE) and normal skin (CENS) caused inhibition to mitochondrial respiration and inner membrane function. Ethyl acetate extracts from CEBE (D1) and CENS (D'1) caused depression of the Respiratory Control Ratio, (RCR), an inhibition of respiration rate in state 3 and stimulation to state 4 respiration. Excellent linear correlations exist between the degree of inhibition to state 3, rate of stimulation to state 4 respiration and the logarithm of doses of D1 and D'1. The effective dose ranges (0.75-0.25 mg/ml for D1 and 4-1 mg/ml for D'1) differ by one order of magnitude. The activity of NADH dehydrogenase and succinate dehydrogenase of mitochondria after incubation with the highest toxic dose of D1 or D'1 remained normal. Dinitrophenol (DNP)-stimulated respiration was moderately inhibited by D1 and D'1. No change of oligomycin-sensitive ATPase activity was demonstrated. Exogenous malondialdehyde (MDA) did not show any inhibitory effect. Preliminary studies show that D1 contains a family of free fatty acids (FFA). Incubation of normal mitochondria with D1 increased the content of saturated FFA and a decrease of unsaturated FFA. The role of other peroxidative products is under investigation.
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PMID:Inhibition of mitochondrial respiratory function by an organic solvent extractable component from an extract of burn eschar. 183 77

The effects of 5-azacytidine (5-AC) administration on the hepatic cytochrome P-450 systems of mice were studied. A single i.p. dose of 5-AC (25 mg/kg) to male Swiss-Webster mice caused about a 50% depression of microsomal cytochromes P-450 and b5 and of ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities. Depression was greatest 24 h after treatment; by 48 to 72 h, cytochromes and drug metabolism had returned to near control values. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also depressed by 5-AC, whereas reduced nicotinamide adenine dinucleotide-cytochrome c reductase was not. Incubation of 5-AC with microsomes produced no effect on drug metabolism. The prolongation of hexobarbital sleeping time by 5-AC showed that drug metabolism is also impaired by 5-AC in vivo. These studies may have important clinical implications when certain drugs are coadministered with 5-AC.
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PMID:Depression of the hepatic cytochrome P-450 monooxygenase system by treatment of mice with the antineoplastic agent 5-azacytidine. 257 31

On the material of early autopsies of the above patients the activity of the following myocardial enzymes was undergone the quantitative histochemical study: succinate, lactate, (beta-oxybutyrate, d-glycerophosphate, glucose 6-phosphate and alcohol dehydrogenase, NAD-diaphorase, catalase, phosphorylase. The increase of the activity of practically all enzymes studied was observed in the myocardial areas with no circulation disturbances. This increase was due to the moderate myocardial hypertrophy. On the contrary, in the areas with a non-even blood supply (ischemia) the decrease of the activity of all oxidative-reductive enzymes was observed. The presence of such foci in the myocardium which occur in 70% cases studied facilitates the development of the ventricular fibrillation with a fatal outcome. The enzyme depression is particularly pronounced against the background of a high alcoholic content.
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PMID:[A histochemical study of enzyme activity in the myocardium of victims of sudden death with small-focal cardiosclerosis]. 259 77

Young adult rats absorbed 50 p.p.m. Cd2+ added to drinking water. After 6 weeks, 3, 6 and 9 months of treatment, the ultrastructural condition of liver, kidney and muscle was observed by electron microscopy. The choice of these tissues was determined by their differences in the capacity to accumulate Cd2+: the liver is able to concentrate a considerable amount of metal, but redistributes it throughout the entire organism, while the kidney collects it in view of its elimination. Muscle contains the least Cd2+. A general regression in mitochondria cristae accompanied by a vesiculation and a fragmentation of endoplasmic reticulum appeared simultaneously in the three tissues, at as early as 6 weeks of treatment, and extended progressively with its continuation supporting evidence of a general attack of the intracellular membrane systems. Cd2+ stimulation of membrane-degrading enzymes such as phospholipases and proteases was suggested. A concomitant diminution in glycogen stores was noted. Active synthesis of neutral lipids, especially cholesterol esters, took place in liver mitochondria of treated rats in collaboration with rough endoplasmic reticulum, and progressively generated a multiplication of electron-transparent inclusions in cytoplasm. Isolated mitochondria from liver, kidney and muscle of Cd2+-treated rats maintained partial energy coupling, but displayed a rapid early fall in cytochrome oxidase followed by a partial restoration after 6 months of treatment, and a progressively slackening of succinate dehydrogenase. Isolated vesicles of liver mitochondria inner membrane of treated rats behaved as intact mitochondria, indicating changes inside the membrane itself. Addition in vitro of the metal ion to mitochondria and also to inner membrane vesicles isolated from control rats revealed that Cd2+ was able to stop completely succinate dehydrogenase, but was totally ineffective on cytochrome oxidase. Membrane fixation of Cd2+ on the flavoprotein or SH associated with succinate dehydrogenase is proposed. Considering the close parallelism of the extensive depression of microsomal NADPH cytochrome c reductase and the rapid fall in mitochondrial cytochrome oxidase, it is suggested that an indirect inhibition process occurs, through Cd2+-induced diminution of a constituent common to all cytochromes in the cell.
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PMID:Mitochondria alterations in Cd2+-treated rats: general regression of inner membrane cristae and electron transport impairment. 293 99

There are two pairs of muscles in each abdominal segment of the crab; one pair of flexors and one pair of extensors. In the early larval stages the muscles have short sarcomeres--a property of fast fibers--and high thin to thick filament ratios--a property of slow fibers. In the adult the abdominal muscles are intermediate and slow, since they have fibers with intermediate and long sarcomeres, high thin to thick filament ratios, low myofibrillar ATPase activity, and high NADH diaphorase activity. The different fiber types are regionally distributed within the flexor muscle. Microelectrode recordings from single flexor muscle fibers in the adult showed that most fibers are supplied by three excitatory motor axons, although some are supplied by as many as five efferents. One axon supplies all of the flexor muscle fibers in its own hemisegment, and the evoked junctional potentials exhibit depression. This feature together with the innervation patterns of the fibers are similar to those reported for the deep flexor muscles of crayfish and lobsters. Therefore, in the adult crab, the abdominal flexor muscles have some features in common with the slow superficial flexors of crayfish and other features in common with the fast deep flexor muscles.
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PMID:Neuromuscular relationships in the abdomen of the Californian shore crab Pachygrapsus crassipes. 298 47

The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 micrograms.h-1 GH decreased the total cytochrome P-450 by 16%; at 10 micrograms.h-1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-turnover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast:slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p less than 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.
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PMID:Growth hormone depresses ethylmorphine demethylase activity: correlation with decreased levels of fast-turnover cytochrome P-450 in hypophysectomized female rats. 314 99

Treatment of mice and rats with polyriboinosinic acid-polyribocytidylic acid (poly I.C., 5 mg/kg i.p.), a potent interferon inducer, decreased hepatic cytochrome P-450 system content and activities without influencing P-450-independent xenobiotic metabolizing enzymes. Treatment with poly I.C. decreased the content of P-450 by 28% in mice (P less than 0.05) and 30% in rats (P less than 0.05) but did not alter the activity of cytochrome c reductase. With treatment of poly I.C., the activity of XO increased 87% in mice (P less than 0.01) and 30% in rats (P less than 0.01). Lipid peroxidation was enhanced by 82% in mice (P less than 0.01) and 95% in rats (P less than 0.05). These results raise the possibility that a part of the depression of P-450 system content and activities by poly I.C. might be caused by enhanced lipid peroxidation associated with increased activity of XO.
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PMID:Treatment with poly I.C. enhances lipid peroxidation and the activity of xanthine oxidase, and decreases hepatic P-450 content and activities in mice and rats. 375 66


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