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)

Fluorescence techniques may be utilized to map changes in the distribution of mitochondrial redox states in heart and brain during ischemic or hypoxic stress. The basis of these techniques is the intrinsic fluorescence of reduced NADH and oxidized flavoprotein in mitochondria which respond to changes in critical oxygen supply. Ischemic areas in rabbit hearts induced by coronary ligation were detected and mapped based on the increase in NADH fluorescence in the ischemic zone. The width of the jeopardized normoxic tissue surrounding the ischemic area (less than 50--350 mu) was measured by combination of fluorescein angiography and NADH fluorescence. Areas of increased NADH fluorescence in gerbil brains after carotid artery ligation or induction of spreading depression were mapped in a similar manner. Intraoperative monitoring of flavoprotein fluorescence from human cerebral cortex after superficial temporal artery middle cerebral artery (STA-MCA) anastomoses demonstrated increased rates of cortical oxidative metabolism after the surgical procedures.
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PMID:Fluorescence mapping of mitochondrial redox changes in heart and brain. 22 13

Human red cells were incubated at pH 8.2 and 30 mM phosphate concentration with glucose, glucose plus methylene blue, or inosine. In 16 normal subjects, the lactate production rate (LPR) from glucose alone was 92.2 +/- 7.5 mumoles per minute per liter red blood cell. With methylene blue added, the mean LPR was 118.5 +/- 7.4 per cent of control glucose values. With inosine as substrate the mean LPR was 68.5 +/- 6.0 per cent of that from glucose. Lactate/glucose ratios averaged 1.36, presumably because of accumulation of intermediates under conditions of high pH and Pi. Patients with various kinds of anemias had LPR's from glucose that were usually markedly higher than normal, but the LPR's from inosine were generally about 2/3 of those from glucose. The LPR's of the anemic patients correlated with their degree of reticulocytosis and several patients with pyruvate kinase (PK) deficiency showed normal LPR if the red cell population age was ignored, byt marked depression when compared to expected LPR for degree of reticulocytosis. The LPR from glucose of red cells of G6PD-deficient subjects was decreased (not increased) by methylene blue. Methylene blue, while stimulating the pentose phosphate pathway, also mediated some oxidation of NADH, thus complicating the stoichiometry of the overall system. In addition, the results suggested that the dye may have attacked -SH groups on some enzymes. In normal red cells, the lower LPR from inosine than from glucose was explained as due to consumption of ATP for hexose utilization (thus generating more ADP for the triose reactions). In confirmation, when red cells were incubated without substrate to deplete their ATP-, and enhance their ADP-, levels, the LPR from inosine exceeded that from glucose. Fluoride and iodoacetate affected LPR from glucose more than from inosine, suggesting the necessity of adequate ATP levels in hexose utilization. Overall glycolysis in the red cell is seen as the resultant of a network of metabolic reactions in which ADP and ATP levels are important control parameters.
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PMID:Incubation studies on human red cells utilizing glucose or inosine under various conditions. 24 Aug 98

Ultrastructural morphometric and biochemical studies were conducted on hepatic mitochondria from control rats and rats treated in vivo with arsenate to examine changes in interrelationships between mitochondrial structure and biochemical functions. Morphometric analysis disclosed an over-all 1.2-fold increase in the relative mitochondrial volume density and 1.4-fold increase in the surface density of the inner mitochondrial membrane of arsenate-exposed rats. These structural changes were associated with a 1.5-fold increase in 14C-leucine incorporation into all mitochondrial proteins, which was primarily associated with the acid-insoluble membranous fraction. Mitochondria from arsenate-treated rats showed a marked disruption of normal conformational behavior with depression of nicotinamide adenine dinucleotide (NAD)-linked substrate oxidation and a resulting in vivo increase in the mitochondrial [NAD] to [NADH] ratio. Observed changes in mitochondrial membranes from arsenate exposure also resulted in 1.5- to 2-fold increases in the specific activities of the membrane marker enzymes monoamine oxidase, cytochrome oxidase, and Mg2+-ATPase. Activity of malate dehydrogenase, which is localized in the mitochondrial matrix, was unchanged. The results of this study demonstrate a positive quantitative in vivo correlation between mitochondrial structure and function and indicate a marked dependency upon membrane integrity for normal maintenance of the specific biologic activities performed by this organelle in vivo.
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PMID:Studies of hepatic mitochondrial structure and function: morphometric and biochemical evaluation of in vivo perturbation by arsenate. 49 44

We have developed the multiprobe assembly (MPA) by which metabolic, ionic and electrical activities can be monitored from the surface of the brain. In the present study we included optical fibers for the monitoring of intracapillary hemoglobin oxygenation by use of the Erlangen Microlight Guide Spectrophotometer (EMPHO-I) from the surface of the gerbil brain. The newly developed MPA provides simultaneous information about oxygen delivery (oxydeoxy Hb), tissue pO2 level, as well as the intracellular oxygen balance (intramitochondrial redox state). The ionic homeostasis was evaluated by monitoring extracellular K+ and Ca2+ activities reflecting the permeability changes of cation channels as well as the activities of Na+,K(+)-ATPase and other ion linked transport processes. The electrical activities were monitored by a bipolar electrocortical surface probe and DC steady potential. The subjects of the present study were Mongolian gerbils (Meriones unguiculatus) anesthetized and operated according to our routine techniques. After 30 min of recovery from the operation each gerbil was exposed to a short anoxia, graded hypoxia, ischemia as well as spreading depression. The results can be summarized as follows: 1. A clear correlation was recorded between the changes in oxydeoxy Hb spectra, tissue pO2 level and oxidation-reduction state of intramitochondrial NADH under oxygen deficiency situations (hypoxia, ischemia). 2. Blood volume changes under various perturbations monitored by various probes (366 reflectance and EMPHO-I) correlated very well with each other. 3. The degree of inhibition of Na+,K(+)-ATPase induced by oxygen deficiency could be interpreted by changes in extracellular levels of K+ measured by the surface mini-electrode. 4. Brain stimulation induced by spreading depression mechanism led to transient changes in ionic homeostasis and increase in energy requirements. The major HbO2 response was an increase in oxygenation due to the large CBF increase as monitored by the laser Doppler flowmeter. 5. Changes in oxy-deoxy Hb under fast scanning of 500-600 nm during 2-3 seconds of bilateral carotid arterial occlusion provided an indirect index for tissue O2 consumption.
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PMID:Multiparametric evaluation of brain functions in the Mongolian gerbil in vivo. 133 23

Effect of age and phenobarbital on the rat mixed function oxidase activity was studied. Male Wistar rats 0.5-, 1-, 2-, 4-, 8-, 12-, 20- and 28 month-old were used. In this study the levels of cytochrome P-450 and cytochrome b5. NADPH-cytochrome P-450 and NADH-cytochrome b5 reductases activity were examined. Both cytochrome P-450 and NADPH-cytochrome P-450 reductase activity was induced by phenobarbital in all animals. Maximum was observed in 4- and 8-month-old for hemoprotein and 2-month-old rats for reductase activity but minimum in youngest and oldest one respectively. On the contrary, cytochrome b5 and NADH-cytochrome b5 reductase activity was inhibited after phenobarbital injection. The highest depression of cytochrome b5 content was found in youngest, but the enzyme activity in oldest rats.
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PMID:[Effect of age and phenobarbital on liver activity of mixed function oxidase]. 134 96

Isolated hepatocytes from hypothyroid, euthyroid and hyperthyroid rats have been employed to investigate the relative importance of reducing-equivalent shuttles for the transfer of hydrogen between cytoplasm and mitochondria during simultaneous ureogenesis and gluconeogenesis. In cells from hypothyroid animals, a 58% depression of glucose formation and 68% reduction in ureogenesis were induced by n-butylmalonate, an inhibitor of the malate shuttle. A more reduced state of the cytoplasmic compartment and a substantial fall in the concentrations of pyruvate, aspartate, alanine and glutamate accompanied this inhibition. Preincubation of cells with n-butylmalonate yielded greater inhibitory effects than observed in the absence of preincubation. The inhibitory effects on gluconeogenesis and ureogenesis were less in cells from euthyroid rats and were very much reduced in the case of glucose synthesis and absent in the case of ureogenesis, in cells from hyperthyroid rats. It is inferred that both the malate-aspartate and alpha-glycerophosphate shuttles may function in the transfer of reducing equivalents from cytoplasm to mitochondria during ureogenesis in hepatocytes. The major inhibition by n-butylmalonate of glucose and urea synthesis in hepatocytes from hypothyroid rats is due to the diminished activity of the alpha-glycerophosphate shuttle in these cells. Moreover, it follows that the NADH arising from the cytoplasmic malate dehydrogenase-catalysed reaction is accessible to both the malate-aspartate shuttle and the alpha-glycerophosphate shuttle.
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PMID:Reducing-equivalent transfer to the mitochondria during gluconeogenesis and ureogenesis in hepatocytes from rats of different thyroid status. 135 45

Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH-cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down-regulation of mRNA for cytochrome P450 2C11 and 3A2.
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PMID:Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid. 140

The effect of inhibitors of proton pumps, of uncouplers and of permeant ions on the relationship between input force, delta mu H+, and output flows of the ATPase, redox and transhydrogenase H(+)-pumps in submitochondrial particles was investigated. It is concluded that: (1) The decrease of output flow of the transhydrogenase proton pump, defined as the rate of reduction of NADP+ by NADH, is linearily correlated with the decrease of input force, delta mu H+, in an extended range of delta mu H+, independently of whether the H(+)-generating pump is the ATPase or a redox pump, or whether delta mu H+ is depressed by inhibitors of the H(+)-generating pump such as oligomycin or malonate, or by uncouplers. (2) The output flows of the ATPase and of the site I redox H(+)-pumps exhibit a steep dependence on delta mu H+. The flow-force relationships differ depending on whether the depression of delta mu H+ is induced by inhibitors of the H(+)-generating pump, by uncouplers or by lipophilic anions. (3) With the ATPase as H(+)-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by malonate than by uncouplers; the latter, however, are more inhibitory than lipophilic anions such as ClO4-. With redox site I as proton-consuming pump, at equivalent delta mu H+ values, the output flow is more markedly inhibited by oligomycin than by uncouplers; again, uncouplers are more inhibitory than ClO4-. (4) The results provide further support for a delocalized interaction of transhydrogenase with other H(+)-pumps.
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PMID:Flow-force relationships during energy transfer between mitochondrial proton pumps. 164 34

A new in vivo model for studying brain metabolic and haemodynamic oscillatory phenomena during ischaemia is described. In this model acute or chronic occlusion of one or two carotid arteries in the rat is performed. Due to the partial ischaemia developed, oscillations in the level of intramitochondrial pyridine nucleotides (NADH) as well as flavoproteins (Fp) were recorded from the brain by monitoring the fluorescence of these respiratory chain components. The two fluorescent signals (NADH and Fp) were measured by using the time sharing or DC fluorometer/reflectometer. The changes in the reflected light at the excitation wavelengths (366 and 450 nm) were recorded simultaneously. Bilateral carotid artery occlusion induced immediate oscillations (6-9 waves per min) in the mitochondrial redox state as well as in tissue blood volume in both hemispheres. To verify the accuracy of the NADH monitoring system, including the correction technique for haemodynamic and other artifacts, we used the intracarotid artery saline bolus injection approach. The results could be summarized as follows: (1) unilateral carotid artery occlusion resulted in delayed development of oscillations, particularly in the ipsilateral hemisphere; (2) the oscillation phenomenon was reversible if recirculation restarted within 5 min. Occlusion for more than 30 min resulted in irreversible oscillations; (3) the oscillation appearances and intensities were affected by various physiological conditions. Vasoconstriction, induced by hyperoxia, stimulated the oscillations while vasodilation, induced by hypercapnia, depressed them. Anoxia, hypoxia and spreading depression (SD) abolished the oscillations. Glucose injection was not effective.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oscillations of cortical oxidative metabolism and microcirculation in the ischaemic brain. 167 46

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 microns in depth by superfusion with the membrane-permeant indo-1 acetoxy-methyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 microM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18-22 Hz polyspikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.
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PMID:Mechanism underlying protective effect of MK-801 against NMDA-induced neuronal injury in vivo. 171 15


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