Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.37 (malate dehydrogenase)
 4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of NAD-linked alpha-glycerol-3-phosphate dehydrogenase (NAD-G3PDH; EC 1.1.1.8) was depressed by 35% when the thyroid hormone 3,3',5-triiodo-L-thyronine (20 micrograms/liter) was added to the serum-free, hormonally supplemented medium of cultured neonatal rat heart cells. The degree of depression was greater (65%) when the medium contained normal serum levels of hydrocortisone and insulin. There is a dramatic inverse dose-response relationship between triiodothyronine levels and NAD-G3PDH activity. The classic elevation by thyroid hormones of the FAD-linked alpha-glycerol-3-phosphate dehydrogenase (FAD-G3PD; EC 1.1.99.5) was observed concurrently. The medium-glucose depletion rate in triiodothyronine-free cells was depressed 32% through 11 days-in-culture, indicating reduced glycolytic activity. The activities of nine other metabolically important enzymes which were measured during this study, including hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, phosphofructokinase, pyruvate kinase, malate dehydrogenase, NAD-isocitrate dehydrogenase, NADH cytochrome c reductase, and succinic cytochrome c reductase, did not respond to varying triiodothyronine concentrations.
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PMID:Triiodothyronine depresses the NAD-linked glycerol-3-phosphate dehydrogenase activity of cultured neonatal rat heart cells. 669 42

The main objective of this study was to determine whether the principal abnormality of thyroid function observed in patients with chronic renal failure, low serum triiodothyronine (T(3)) concentration, causes hypothyroidism at the tissue level. A partially nephrectomized (Nx) uremic rat model was developed and the following parameters of thyroid function were assessed: serum total thyroxine (TT(4)), total T(3) (TT(3)), and thyrotropin and liver T(3) content, and activity of two thyroid hormone-dependent enzymes, mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) and cytosol malate dehydrogenase (MDH). The results were compared to those of intact control (C), thyroidectomized (Tx), and nephrectomized-thyroidectomized (NxTx) littermates.Results expressed as mean+/-SEM showed that Nx rats had a fivefold increase in blood urea nitrogen, (112+/-20 mg/dl in Nx, and 22+/-1 mg/dl in C) and manifested all the changes of of thyroid function observed in uremic men, including a low serum TT(3) level (30+/-7 ng/dl in Nx and 50+/-6 ng/dl in C). In the liver, T(3) was significantly reduced (18+/-2 ng/total liver in Nx and 35+/-3 ng/total liver in C) as well as the activities of alphaGPD (8.8+/-1.0 and 16.1+/-1.5 DeltaOD/min per total liver in Nx and C, respectively) and MDH (6.3+/-1.6 and 12.6+/-2.2 U/total liver in Nx and C, respectively). The reduction in liver enzyme activities correlated significantly with the decrease in T(3) content. The changes in Tx rats were as expected, showing a profound reduction in serum hormone levels, liver T(3) content, and liver enzyme activities. Serum thyrotropin was markedly elevated to 2,390+/-212 ng/ml as compared to 703+/-61 in C and 441+/-87 ng/ml in Nx rats. The NxTx rats showed the combined effects of nephrectomy and thyroidectomy; blood urea nitrogen was elevated to 203, and serum levels of TT(4), TT(3), and thyrotropin were 0.4, <10, and 2,525, respectively. Total liver T(3) and alphaGPD and MDH were strikingly low; the corresponding values were 3.5, 2.4, and 2.5.l-triiodothyronine replacement (0.4 mug/100 g body wt/d) for 4 wk in the Nx rats resulted in significant increases in liver enzyme activities, alphaGPD and MDH rose by 70 and 60% over their respective basal values without alteration in the severity of azotemia. From these data, we conclude that the reduction of liver T(3) content in the uremic rats, accompanied by a decrease in alphaGPD and MDH activity, indicates the presence of hypothyroidism at the tissue level. Restoration of enzyme activities toward normal levels after T(3) administration provided further supporting evidence that the diminution in liver enzyme activity was causally related to tissue T(3) deficiency.
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PMID:Thyroid function in a uremic rat model. Evidence suggesting tissue hypothyroidism. 677 47

The synthesis of hepatic cytosol malate dehydrogenase (MDH) can be stimulated by thyroid hormones under various conditions, and consequently, this enzyme has been considered as a marker of the expression of thyroid hormone action. Since the concentrations of serum thyroid hormones increase considerably during the late phase of chick embryogenesis, we have studied the relationship between this phenomenon and liver MDH activity. A delay of 5 days was observed between the increase in circulating T4 and T3 concentrations and the enhancement of MDH activity. However, treatment with pharmacological doses of T4 (60 microgram/day) resulted in increased MDH activity 48 h after administration of the hormone, while hypothyroidism induced by methimazole decreased the level of the enzyme. Sex-linked differences in MDH activity were found in newborn chickens between 5-9 days of age. No such differences were observed for serum T3 and T4. These findings suggest that under physiological conditions MDH activity is not directly modulated by thyroid hormones in the chick embryo. However, these hormones may well play a permissive role with this enzyme.
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PMID:Relationship between hepatic malate dehydrogenase and thyroid hormones in the chicken during embryogenesis and the neonatal period. 746 Aug 21

The effects of in vivo treatment with graded doses (0.5-1.5 micrograms/g body weight) of thyroid hormones, tri-iodothyronine (T3) and thyroxine (T4), for 4 consecutive days to euthyroid rats on the respiratory activity of isolated brain mitochondria were examined. T4 stimulated coupled State-3 respiration with glutamate, pyruvate + malate, ascorbate + tetramethyl-p-phenylenediamine and succinate, in a dose-dependent manner; T3 was effective only at the highest (1.5 micrograms) dose employed. T4 was more effective than T3 in stimulating respiratory activity. State-4 respiratory rates were in general not influenced except in the case of the ascorbate + tetramethyl-p-phenylenediamine system. Primary dehydrogenase activities, i.e. glutamate dehydrogenase, malate dehydrogenase and succinate dehydrogenase, were stimulated about 2-fold; interestingly mitochondrial but not cytosolic malate dehydrogenase activity was influenced under these conditions. The hormone treatments did not greatly influence the mitochondrial cytochrome content. The results therefore suggest that thyroid hormone treatment not only stimulates primary dehydrogenase activities but may also directly influence the process of mitochondrial electron transfer.
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PMID:Is respiratory activity in the brain mitochondria responsive to thyroid hormone action?: a critical re-evaluation. 794 13

The mitochondrial phenotype within cardiac muscle cells is dramatically altered by thyroid hormone. We report here that this can be accounted for, in part, by modifications in the rate of mitochondrial protein import. The import of matrix-localized precursor proteins malate dehydrogenase (MDH) and ornithine carbamoyltransferase was augmented, whereas the insertion of the outer membrane protein Bcl-2 was unaffected by thyroid hormone treatment. Coincident with increases in the import of these matrix-localized precursors were thyroid hormone-induced elevations in the outer membrane receptor Tom20 and the matrix heat-shock protein mthsp70. The phospholipid cardiolipin was not involved in mediating the thyroid hormone-induced increase in import, as judged from adriamycin inhibition studies. When the import reaction was supplemented with rat heart cytosol, we found that 1) MDH import was stimulated, but Bcl-2 import was inhibited and 2) thyroid hormone did not influence the effect of the cytosol on import rates. Thus distinct requirements exist for the mitochondrial import of precursor proteins, destined for different organellar compartments. Although import of these matrix-localized proteins was augmented by thyroid hormone treatment, the proteolysis of matrix proteins was unaffected as indicated by the degradation of cytob2(167)RIC-dihydrofolate reductase, a chimeric protein missorted to the matrix. Thus our data indicate that at least some thyroid hormone-induced modifications of the mitochondrial phenotype occur due to the compartment-specific upregulation of precursor protein import rates, likely mediated via changes in the expression of protein import machinery components.
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PMID:Thyroid hormone modifies mitochondrial phenotype by increasing protein import without altering degradation. 984 12

Mitochondrial biogenesis is accompanied by an increased expression of components of the protein import machinery, as well as increased import of proteins destined for the matrix. We evaluated the role of the outer membrane receptor Tom20 by varying its expression and measuring changes in the import of malate dehydrogenase (MDH) in differentiating C2C12 muscle cells. Cells transfected with Tom20 had levels that were twofold higher than in control cells. Labeling of cells followed by immunoprecipitation of MDH revealed equivalent increases in MDH import. This parallelism between import rate and Tom20 levels was also evident as a result of thyroid hormone treatment. Using antisense oligodeoxynucleotides, we inhibited Tom20 expression by 40%, resulting in 40-60% reductions in MDH import. In vitro assays also revealed that import into the matrix was more sensitive to Tom20 inhibition than import into the outer membrane. These data indicate a close relationship between induced changes in Tom20 and the import of a matrix protein, suggesting that Tom20 is involved in determining the kinetics of import. However, this relationship was dissociated during normal differentiation, since the expression of Tom20 remained relatively constant, whereas imported MDH increased 12-fold. Thus Tom20 is important in determining import during organelle biogenesis, but other mechanisms (e.g., intramitochondrial protein degradation or nuclear transcription) likely also play a role in establishing the final mitochondrial phenotype during normal muscle differentiation.
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PMID:Tom20-mediated mitochondrial protein import in muscle cells during differentiation. 1102 87

We studied the rat thyroid status depending on the dose of external radiation and the time passed after the exposure. The experiments were carried out on female albino Wistar rats. The doses absorbed amounted to 0.25; 0.5; 1.0; 2.0 and 5.0 Gy. The animals were decapitated after 3, 6, 24 hours and 7, 30, 180 and 365 days following the radiation. The blood serum was assayed for the contents of thyroxin (T4) and triiodothyronine (T3) using a radioimmunological technique. The liver tissue was assayed spectrophotometrically for the activity of thyroid-induced NADP malate dehydrogenase (NADP-MDH). No changes were found in the blood thyroid hormone contents within short periods after the radiation effect. After 6 hours the T4 levels was 1.2-1.3-fold decreased in the blood of rats receiving the radiation doses of 1.0; 2.0; and 5.0 Gy. After a day the T4 concentration was diminished by 1.21-193-fold in all the experimental animals independently of the radiation dose and that of T3--in 2.0 Gy--and 5.0 Gy--irradiated group. After 7 days following the radiation the T4 and T3 contents remained to be decreased by 1.37-1.75 fold and those of NADP-MDH--by 1.3-1.8-fold in all the animal groups. In a month, the low dose-treated animals (0.25, 0.5, 1.0 Gy) showed the level of thyroid hormones reduced to the control values, whereas the 2.0 and 5.0 Gy--treated rats demonstrated this reduction only by 6 months. The decreased concentration of blood thyroid hormones was due not to the activation of their peripheral metabolism, but, probably, to inhibition of their biosynthesis in thyroid cells under conditions of radiation-induced activation of oxidative stress.
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PMID:[Effects of single-dose external gamma irradiation on rat thyroid status as observed during the year]. 1267 61

We have investigated the effect of thyroid hormone on the mitochondrial membrane permeability properties in a hypothyroid rat model. The role played by calcium in affecting these properties has been also examined. Cyclosporin A-sensitive mitochondrial calcium efflux, swelling, and external release of matrix proteins are events that occur normally during the permeability transition process induced by calcium loading of mitochondria. We demonstrate that these events are impaired in mitochondria isolated from the liver of hypothyroid rats, even in the presence of high calcium content. However, after thyroid hormone administration to hypothyroid rats, the mitochondrial permeability transition process in response to calcium loading is restored. Consequently, mitochondrial calcium efflux, swelling, and release of matrix proteins, like glutamate dehydrogenase, malate dehydrogenase, and aspartate aminotransferase occur. These effects are abrogated by the concomitant administration of cyclosporin A. The results of the present study suggest that hypothyroidism may be a potential source of adverse effects in patients receiving cyclosporin A.
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PMID:Thyroid hormone administration to hypothyroid rats restores the mitochondrial membrane permeability properties. 1293 49

The effect of long-term exposure to low-dose external radiation on the rat thyroid status was studied. The experiments were carried out on Wistar female rats. The single doses absorbed were 0.1; 0.25; 0.5 Gy. The rats were irradiated 20 times (5 days x 4 weeks). The animals were decapitated after 1, 30 and 180 days following the last irradiation. Blood serum was assayed for content of thyroxin (T4) and triiodothyronine (T3) radioimmunologically. The liver was spectrophotometrically assayed for thyroid-induced NADP-malatedehydrogenase (NADP-MDH). It was shown that the long-term 0.5-Gy irradiation of the animals induced a decrease in blood T4 and T3 concentrations 1.34-1.71-fold and 1.24-1.43-fold after 1, 30 and 180 days, respectively. The T3 level was diminished most pronouncedly after 1 day, whereas that of T4--after 30 days following the exposure. With the doses of 0.1 and 0.25 Gy absorbed, the T4 and T3 concentration remained unchanged throughout all the periods studied. The activity of NADP-MDH was decreased 1.55-2.46-fold in all the experimental animals, and it was held decreased after 180 days (1.43-1.50-fold) in 0.25- and 0.5-Gy-irradiated groups, which indicates a disturbance in thyroid hormone metabolism in rats exposed chronically to low-dose radiation. After 180 days, the experimental animals experienced an elevation of thyroid gland weight on 15-20%. The thyroid status disturbance seemed to be due to both inhibited T4 and T3 biosynthesis in thyroid and disturbed hormone peripheral metabolism under radiation exposure.
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PMID:[Effect of long-term exposure to low dose gamma-irradiation on the rat thyroid status]. 1506 Sep 46

We have investigated the effect of thyroid hormone on recovery of liver mass and on the mitochondrial membrane permeability properties during rat liver regeneration after 70% partial hepatectomy (PH). In the euthyroid state, liver weight starts to recover 24 h after PH and is completely restored 96 h after PH. Cyclosporin A (CsA)-sensitive mitochondrial permeability transition (MPT) occurs 24 h after PH, and it has been suggested to act in the signaling mechanism for hepatocyte proliferation. In this study we show that hypothyroidism delays recovery of the liver mass, being only 50% of the initial weight 96 h after PH, and alters the duration and mode of MPT occurrence, first inducing a CsA-insensitive swelling 24 h after PH, followed by a CsA-sensitive swelling 96 h after PH. The occurrence of both CsA-sensitive and -insensitive swelling is shown to be associated with an increase in mitochondrial calcium content. Concurrent with mitochondrial swelling, external release of matrix proteins from mitochondria, such as aspartate aminotransferase and malate dehydrogenase, is shown to be CsA insensitive 24 h after PH and CsA sensitive 96 h after PH. After thyroid hormone administration to hypothyroid rats, the liver regenerative capacity is restored, and the duration and mode of MPT occurrence as well as changes in mitochondrial calcium content become similar to those observed in the euthyroid condition. The results of the present study suggest the involvement of a mitochondria-mediated pathway in regulation of the liver regenerative process by thyroid hormone.
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PMID:Thyroid hormone treatment of hypothyroid rats restores the regenerative capacity and the mitochondrial membrane permeability properties of the liver after partial hepatectomy. 1530 17


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