Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many animal and in vitro experiments have shown that the supplementation of diet with vitamin E within a certain dose range reduced the risk of chemical- and radiation-induced cancers. In vitro studies revealed that alpha-tocopheryl succinate (TS) induced differentiation and growth-inhibition in certain animal and human tumor cells in culture, whereas alpha-tocopherol (alpha-T), alpha-tocopheryl acetate (alpha-TA) and alpha-tocopheryl nicotinate (alpha-TN) were ineffective, alpha-TS also reduced basal and ligand-stimulated adenylate cyclase activity, and expression of c-myc and H-ras oncogenes in certain tumor cells in culture. The relative efficacy of various forms of vitamin E in cancer prevention in animal or human models has not been evaluated. Human epidemiologic studies utilizing retrospective and prospective case-control experimental designs are not suitable for evaluating the role of vitamin E in cancer prevention due to several inherent problems associated with these methodologies. Intervention trials utilizing vitamin E with appropriate biological and statistical rationales are most suitable for testing the role of vitamin E in cancer prevention in humans. Some human trials utilizing vitamin E alone or in combination with other nutrients are in progress.
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PMID:Vitamin E and cancer prevention: recent advances and future potentials. 840 88

It was found that calcium exchange disturbances under vitamin E deficiency is due to changes in the metabolism of vitamin D. In vitamin E-deficient rats the serum blood levels of hydroxyvitamin D (25-OHD) showed no significant changes, whereas the concentration of the hormonal form of 1.25-hydroxyvitamin D [1.25(OH)2D], decreased by 40%. In vitro studies showed that the 25-hydroxylase D3 activity in the livers of rats with E-avitaminosis had a tendency to decrease (by 22%), whereas that of 24-hydroxylase dropped drastically (by 52%). The serum blood levels of the parathyroid hormone (PTH) and kidney levels of cAMP under E-avitaminosis were significantly lowered. Preincubation of kidney slices with the adenylate cyclase activator, forskolin, increased the activity of 1-OHase in about the same degree as that in vitamin E-rich rats. The free radical scavenger, BHT, added to kidney slices suppressed the activity of the both enzymes; this finding testifies to the low O2-binding affinity of these monooxygenases. The content of 1.25(OH)2D3 receptors occupied in vivo in the kidneys of vitamin E-deficient rats decreased 2.5-fold; however, the binding of 1.25(OH)2D3-receptor complexes to heterologous DNA was unaffected thereby. The vitamin deficiency in vivo results in the inhibition of vitamin D metabolism in the liver and kidney concomitant with the formation of active metabolites and decreases the concentration of hormone-receptor complexes in target tissues.
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PMID:[The role of vitamin E in metabolism and reception of vitamin D]. 196 7

Alpha tocopheryl succinate treatment (6-8 micrograms/ml), which inhibited the growth of murine neuroblastoma (NBP2) cells (46 +/- 3%), reduced basal and prostaglandin (PG)E1- and PGA2-stimulated adenylate cyclase (AC) activity in vitro. It also inhibited sodium fluoride (NaF)- and forskolin-stimulated AC activity, suggesting that the effect of vitamin E succinate on AC activity is mediated via stimulatory GTP-binding protein (Gs) and catalytic subunit. Vitamin E succinate-induced reduction of AC activity is not strictly related to inhibition of cell growth. This is substantiated by the finding that, although retinoic acid and butylated hydroxyanisole reduced the growth by over 50%, they did not inhibit AC activity. On the other hand, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, 200 micrograms/ml), which inhibited growth (73 +/- 3%) and induced differentiation in NB cells, increased basal and PGE1-stimulated AC activity. Vitamin E succinate treatment also reduced PGE1- and PGA2-AC activity in murine fibroblasts (L-cells) without inhibiting growth.
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PMID:Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture. 320 80

D-alpha tocopheryl succinate (vitamin E succinate), which is known to induce differentiation and growth inhibition in murine B-16 melanoma cells, reduced basal and melanocyte-stimulating hormone (MSH)-stimulated adenylate cyclase (AC) activity in vitro. Vitamin E succinate treatment also reduced sodium fluoride- and forskoline-stimulated AC activity of melanoma cells in vitro. Treatment of cells with vitamin E succinate (6 micrograms/ml] for a period of 24 hours was sufficient to reduce MSH-stimulated AC activity. Other forms of vitamin E, such as d1-alpha tocopheryl nicotinate, d1-alpha tocopheryl acetate, and d1-alpha tocopherol, which did not affect growth or morphology of melanoma cells, were relatively less effective in altering basal and MSH-stimulated AC activity. Retinoic acid, which inhibited the growth of B-16 melanoma cells, also reduced basal and MSH-, NaF-, and forskolin-stimulated AC activity in vitro. Prostaglandin A2, which inhibited growth and altered morphology, did not change basal or MSH-stimulated AC activity. These results show that one of the mechanisms of action of vitamin E succinate and retinoic acid on melanoma cells may involve reduction of basal and MSH-sensitive AC activity, and this vitamin effect is not necessarily related to growth inhibition.
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PMID:Alpha tocopheryl succinate inhibits melanocyte-stimulating hormone (MSH)-sensitive adenylate cyclase activity in melanoma cells. 369 13

The effect of heat in combination with DL-alpha-tocopheryl (vitamin E) succinate and adenosine 3', 5'-cyclic monophosphate (cAMP) stimulating agents on mouse neuroblastoma cells ( NBP2 ) in culture on the criterion of growth inhibition (due to cell death and inhibition of cell division) was studied. Heat (41 degrees-40 degrees) alone inhibited growth; however, the extent of growth inhibition was dependent upon the temperature and the time of heat treatment. Heat (41 degrees-40 degrees) in combination with vitamin E succinate (5 micrograms/ml) produced an additive effect on the criterion of growth inhibition. Vitamin C (100 micrograms/ml) failed to modify the effect of heat. Prostaglandin A2, a stimulator of adenylate cyclase, and 4 - (3-butoxy-4-methoxybenzyl)-2-imidazolidinone ( R020 -1724), an inhibitor of cyclic nucleotide phosphodiesterase, are known to induce irreversible differentiation in mouse neuroblastoma cells in culture. These agents, in combination with heat (40 degrees) produced a synergistic effect on the criterion of growth inhibition. These data suggest that the addition of vitamin E and cAMP stimulating agents may increase the effectiveness of hyperthermia protocol.
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PMID:Effect of hyperthermia in combination with vitamin E and cyclic AMP on neuroblastoma cells in culture. 632 55

The paper deals with studies into the mechanism of hepatoprotective action of essential phospholipids (EP) in chronic alcohol intoxication. EPs reduce the count of hepatocytes with hypotopic and fatty dystrophic signs, normalize hepatic triglycerides. The EP antioxidative effect found is associated with vitamin E admixture in the preparation. EPs reduce the level of cAMP and the activity of adenylate cyclase. The activity of cAMP-dependent protein kinase becomes normal only with high doses of EP (300 mg/kg). It is suggested that the hepatoprotective effect of EP may be manifested through normalization of the cAMP-dependent transduction of a signal, resulting in stabilization of hepatic metabolic processes.
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PMID:[Effect of essential phospholipids on the structural and metabolic changes in the rat liver in experimental alcoholic intoxication]. 770 Jul 4

Previous studies have shown that vitamin E supplementation inhibits murine melanoma cell growth in vitro. In this study, malignant murine melanoma (BL6) and non-malignant monkey kidney (LLCMK) cells were supplemented with 1-10 micrograms/ml D-alpha-tocopherol acid succinate (vitamin E succinate). The effect of vitamin E succinate supplementation on growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. Results from these studies indicated a significant inhibition of BL6 cell growth at 5 (P < 0.025), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate supplementation, while LLCMK cells showed no significant increase or decrease in growth following vitamin E succinate supplementation. BL6 cells supplemented with 7 and 10 micrograms/ml vitamin E succinate showed a marked increase in PGE2 levels, with a significant increase (P < 0.025) occurring at 10 micrograms/ml. Adenylate cyclase activity in BL6 cells was also significantly increased at vitamin E succinate concentrations of 7 (P < 0.05) and 10 micrograms/ml (P < 0.05), respectively, and supplementation of these cells with 5 (P < 0.05), 7 and 10 micrograms/ml (P < 0.001) vitamin E succinate resulted in a significant increase in the levels of cAMP, while LLCMK cells showed no significant increase or decrease in PGE2, adenylate cyclase activity or cAMP levels over the vitamin concentrations tested.
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PMID:The role of adenylate cyclase, cAMP and PGE2 in the in vitro growth regulation of murine melanoma cells by vitamin E. 883 67

Malignant murine melanoma (BL6) cells cultured in vitro were supplemented with indomethacin (0.15 microM) and varying levels (1-10 micrograms/ml) of vitamin E succinate. The effect of combined indomethacin and vitamin E succinate treatment on the growth as well as the levels of adenylate cyclase activity, prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) were determined in these cells. BL6 cells supplemented with 0.15 microM indomethacin and 1-10 micrograms/ml vitamin E succinate showed a significant (P < or = 0.05) decrease in growth at 1 microgram/ml vitamin E succinate, while at 3-10 micrograms/ml, no significant increase or decrease in growth was observed when compared to control cultures (OE). Results from studies of adenylate cyclase activity in BL6 cells showed no significant increase or decrease in enzyme activity, nor were the levels of PGE2 and cAMP affected when the cells were supplemented with 0.15 microM indomethacin and 1-10 micrograms/ml vitamin E succinate.
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PMID:Effect of vitamin E and indomethacin treatment on adenylate cyclase activity, PGE2 and cAMP levels in murine melanoma cells. 905 24

Numerous articles and several reviews have been published on the role of antioxidants, and diet and lifestyle modifications in cancer prevention. However, the potential role of these factors in the management of human cancer have been largely ignored. Extensive in vitro studies and limited in vivo studies have revealed that individual antioxidants such as vitamin A (retinoids), vitamin E (primarily alpha-tocopheryl succinate), vitamin C (primarily sodium ascorbate) and carotenoids (primarily polar carotenoids) induce cell differentiation and growth inhibition to various degrees in rodent and human cancer cells by complex mechanisms. The proposed mechanisms for these effects include inhibition of protein kinase C activity, prostaglandin E1-stimulated adenylate cyclase activity, expression of c-myc, H-ras, and a transcription factor (E2F), and induction of transforming growth factor-beta and p21 genes. Furthermore, antioxidant vitamins individually or in combination enhance the growth-inhibitory effects of x-irradiation, chemotherapeutic agents, hyperthermia, and biological response modifiers on tumor cells, primarily in vitro. These vitamins, individually, also reduce the toxicity of several standard tumor therapeutic agents on normal cells. Low fat and high fiber diets can further enhance the efficacy of standard cancer therapeutic agents; the proposed mechanisms for these effects include the production of increased levels of butyric acid and binding of potential mutagens in the gastrointestinal tract by high fiber and reduced levels of growth promoting agents such as prostaglandins, certain fatty acids and estrogen by low fat. We propose, therefore, a working hypothesis that multiple antioxidant vitamin supplements together with diet and lifestyle modifications may improve the efficacy of standard and experimental cancer therapies.
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PMID:High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. 1006 54

Previously we have shown that both insufficient (combined with vitamin E deficiency) and excess intake of selenium (Se) impairs isoproterenol (ISO)-induced contractions of rat papillary muscle. In the present study, we used patch-clamp and biochemical techniques to investigate mechanisms of this effect in rats fed a Se- and vitamin E-deficient, a Se-excess or a normal diet. Whole-cell configuration of patch-clamp technique was used to investigate L-type Ca(2+) currents (I(Ca,L)) and their regulation by beta-adrenergic receptor stimulation in enzymatically isolated single rat ventricular myocytes. Alteration of Se and vitamin E intake did not affect peak I(Ca,L), but the threshold potential of activation was significantly different among groups. Maximal I(Ca,L) responses to ISO were depressed in both experimental groups, but the EC(50) values were not affected. In the Se-deficient group, basal, ISO- or forskolin-induced adenylate cyclase (AC) activity, measured in cardiac membrane preparations, was reduced when compared to the control, whereas 5' guanylyimidodphosphate (GppNHp) stimulated activity was unaffected. Decreased beta-adrenoceptor density and reduced GppNHp-induced affinity shift in ISO binding were also observed in the deficient group. No such differences were present in the excess group. These results suggest that combined Se and vitamin E deficiency interferes with beta-adrenoceptor-AC coupling, whereas excess intake of Se does not affect it. Thus, in the deficient group, the impairment of I(Ca) responses to ISO may be a result of a defect in beta-adrenoceptor-AC pathway. Impairment of I(Ca) response in the excess group, however, appears to have a different underlying mechanism.
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PMID:Dietary selenium and vitamin E intakes alter beta-adrenergic response of L-type Ca-current and beta-adrenoceptor-adenylate cyclase coupling in rat heart. 1073 22


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