Search PubMed⌕ Search

Biomedical subjects

T Ramasarma

Publications and source records attributed to T Ramasarma.

At least 55 records · Page 3Linked to original sources
PubMed1991

The nature of inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by garlic-derived diallyl disulfide.

A concentration dependent inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase was found on preincubation of microsomal preparations with diallyl disulfide, a component of garlic oil. This inhibited state was only partially reversed even with high concentrations of DTT. Glutathione, a naturally occurring reducing thiol agent, was ineffective. The substrate, HMG CoA, but not NADPH, was able to give partial protection for the DTT-dependent, but not glutathione-dependent activity. The garlic-derived diallyl disulfide is the most effective among the sulfides tested for inhibition of HMG CoA reductase. Formation of protein internal disulfides, inaccessible for reduction by thiol agents, but not of protein dimer, is likely to be the cause of this inactivation.

Allyl Compounds↗
PubMed1990

Investigations on the mechanism of the hypocholesterolemic action of 1-ethoxysilatrane.

Intraperitoneal administration of the nontoxic silicon compound, 1-ethoxysilatrane, to the rat did not cause proliferation of hepatic mitochondria or of endoplasmic reticulum, nor did it affect mitochondrial oxidative phosphorylation. The activities of cholesterol 7 alpha-hydroxylase in hepatic microsomes and of cholesterol oxidase in mitochondria respectively were unaffected by silatrane treatment. The rate of release of bile, whose composition remained unchanged, also was not increased in silatrane-treated animals. The results indicated that the compound did not affect the pathway of cholesterol degradation. A progressive decrease in the activity of hepatic microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase was observed on administration of the compound over a period of three weeks. Consistent with this, cholesterol biosynthesis in liver as measured by incorporation of radioactive precursors, acetate and water but not mevalonate, was significantly decreased in silatrane-treated animals. However, enzyme-linked immunosorbent assay revealed that the concentration of HMGCoA reductase protein was not decreased by the treatment indicating that inactivated enzyme was also present in such microsomes. Addition of silatrane to microsomes in the assay system did not cause inhibition indicating that the inactivation is by an indirect mechanism. It is concluded that the hypocholesterolemic action of the compound rested entirely on the inhibition of cholesterol biosynthesis in vivo by inactivation of the rate-limiting enzyme HMGCoA reductase.

AMP-Activated Protein Kinases↗
PubMed1990

Decavanadate acts like an alpha-adrenergic agonist in redistributing protein kinase C activity.

Perfusion of rat livers with polyvanadate, but not metavanadate, was found to increase in plasma membrane and decrease in cytosol protein kinase C activity, similar to that obtained with phenylephrine, an alpha-adrenergic agonist. The effect was prevented by phenoxybenzamine, but not by propranolol implicating alpha-adrenergic receptor activation. Comparison of crystal structures of decavanadate and nonadrenaline revealed the occurrence of a structural feature of O-O-O(N) with distances of 5.5 A and 2.9 A.

Adrenergic alpha-Agonists↗
PubMed1990

Decrease of oxidative activities in brown adipose tissue mitochondria of cold acclimated rats on short term exposure to heat stress.

Exposure of rats to the cold (4-5 degrees C) caused large (2-3-fold) increases in the mass of interscapular brown adipose tissue (BAT), its mitochondrial content and the basal metabolic rate of the animals. The rate of substrate oxidation by BAT mitochondria also increased about 3-fold. When cold-acclimated animals were exposed to heat (37 degrees C), the BMR decreased by half in 3 h, the earliest time interval tested. Mitochondrial substrate oxidation, as well as substrate-dependent H2O2 generation, showed a proportionate decrease in rates. In these mitochondria, activities of cytochrome c reductases, but not dehydrogenases with NADH, alpha-glycerophosphate and succinate as substrates, also showed a significant decrease. The concentration of cytochromes aa3 and b, but not cytochrome c, also decreased in BAT mitochondria from 12-h heat-exposed animals, while the change in concentration of cytochrome b alone was found as early as 3 h of heat exposure. These results identify the change in cytochromes as a mechanism of regulation of oxidative activities in BAT mitochondria under conditions of acute heat stress.

Adaptation, Physiological↗
PubMed1990

Increase in hepatic microsomal lipid peroxidation mediated by alpha-adrenergic system under cold stress and noradrenaline treatment.

Lipid peroxidation measured both by the formation of malondialdehyde and by oxygen uptake in presence of NADPH, Fe2+ and ADP in hepatic microsomes increased on cold exposure and decreased on heat exposure of rats. Malondialdehyde content of isolated microsomes also showed similar changes. Treatment of animals with noradrenaline or a alpha-adrenergic agonist, phenylephrine, increased lipid peroxidation which was prevented by simultaneous treatment with cycloheximide, a protein synthesis inhibitor. Cold- and noradrenaline-induced increases were not found in animals pretreated with alpha-adrenergic receptor antagonist, phenoxybenzamine, but not with propranolol, a beta-adrenergic blocking agent. The concentration of the microsomal cytochromes P-450 and b5 remained unaffected under these conditions but the activity of NADPH-cytochrome c reductase showed parallel changes. These observations suggest a role for lipid peroxidation in cellular thermogenesis in liver tissue.

Adrenergic alpha-Antagonists↗
PubMed1990

Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450.

The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis.

Acetates↗
PubMed1990

H2O2 has a role in cellular regulation.

H2O2, in addition to producing highly reactive molecules through hydroxyl radicals or peroxidase action, can exert a number of direct effects on cells, organelles and enzymes. The stimulations include glucose transport, glucose incorporation into glycogen, HMP shunt pathway, lipid synthesis, release of calcium from mitochondria and of arachidonate from phospholipids, poly ADP ribosylation, and insulin receptor tyrosine kinase and pyruvate dehydrogenase activities. The inactivations include glycolysis, lipolysis, reacylation of lysophospholipids, ATP synthesis, superoxide dismutase and protein kinase C. Damages to DNA and proteoglycan and general cytotoxicity possibly through oxygen radicals were also observed. A whole new range of effects will be opened by the finding that H2O2 can act as a signal transducer in oxidative stress by oxidizing a dithiol protein to disulphide form which then activates transcription of the stress inducible genes. Many of these direct effects seem to be obtained by dithiol-disulphide modification of proteins and their active sites, as part of adaptive responses in oxidative stress.

Adenosine Triphosphate↗
PubMed1990

Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat.

Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT.

Acclimatization↗
PubMed1990

Regulation of respiratory activity of brown adipose tissue mitochondria through changes in cytochromes.

Exposure of cold-acclimatized rats to heat (37 degrees C) for a short period decreased brown adipose tissue (BAT) mitochondrial substrate-dependent oxygen uptake and H2O2 generation. Both the concentration and substrate-dependent rate of cytochrome b reduction decreased as early as 3 h of heat exposure. These results identify cytochrome b as the locus of regulation of electron transport in BAT mitochondria under conditions of heat stress.

Adipose Tissue, Brown↗
PubMed1989

Redistribution of subcellular calcium in rat liver on administration of vanadate.

Mitochondria isolated from the livers of rats administered with sodium meta-, ortho-, or polyvanadate, but not vanadyl sulphate, exhibited enhanced Ca2+ -stimulated respiration and uptake of calcium. These effects were shown also by mitochondria isolated from livers perfused with polyvanadate. The concentration of acid-soluble calcium decreased significantly in the mitochondrial fraction on vanadate treatment, while that in the cytosol showed a corresponding increase. Phenoxybenzamine, an antagonist to alpha-adrenergic receptors, effectively inhibited vanadate-induced Ca2+ mobilization, but surgical sympathectomy was without effect. This is the first demonstration of vanadate mimicking alpha-adrenergic agonists in vivo.

Adrenergic alpha-Antagonists↗
PubMed1989

Mevalonate-metabolizing enzymes in Arachis hypogaea.

The activities of the mevalonate metabolizing enzymes-HMG-CoA reductase, mevalonate kinase, mevalonate phosphokinase and mevalonate pyrophosphate decarboxylase -were assayed with the respective substrates in green seedlings of Arachis hypogaea. MVAPP decarboxylase is the rate-limiting step among these enzymes and is inhibited by phenolic acids. Its activity in the seedlings was found to decrease in the absence of light and on treatment with abscisic acid. These results suggest that regulation of isoprene pathway in groundnut seedlings may occur at the level of mevalonate decarboxylation.

Abscisic Acid↗
PubMed1989

Increase in alpha-glycerophosphate dehydrogenase and other oxidoreductase activities of hepatic mitochondria on administration of vanadate to the rat.

Liver mitochondria isolated from vanadate-administered rats showed increased (20-25%) rates of oxidation of both NAD(+)-linked substrates and succinate. Respiratory control index and ADP/O were unaffected by the treatment. Dormant and uncoupler-stimulated ATPase activity also was not affected by vanadate administration. Membrane-bound, electron-transport-linked dehydrogenase activities (both NAD(+)- and succinate-dependent) increased by 15-20% on vanadate treatment. Mitochondrial alpha-glycerophosphate dehydrogenase activity increased by 50% on vanadate administration. The above effects of vanadate on oxidoreductase activities could be prevented by the prior administration of antagonists to alpha-adrenergic receptors. Substrate-dependent H2O2 generation by mitochondria also showed an increase on vanadate administration.

Animals↗
PubMed1988

Oxidative activities in mitochondria-like particles from Setaria digitata, a filarial parasite.

The oxidative metabolic potential of Setaria digitata, a filarial parasite found in the intraperitoneal cavity of cattle, was investigated. These worms showed active wriggling movements which were not affected by respiratory poisons such as cyanide, rotenone and malonate. They also possessed cyanide-insensitive and glucose-independent oxygen consumption pathways. By differential centrifugation of sucrose homogenates, a fraction containing mitochondria-like particles was obtained in which the activity of the marker enzyme, succinate dehydrogenase, was recovered. This fraction catalysed succinate- and NADH-dependent reduction of both cytochrome c and dyes. Oxygen uptake found with succinate, NADH and ascorbate as substrates was not sensitive to cyanide. Cytochromes could not be detected in either this fraction or homogenates of the worms. H2O2 generation with a number of substrates and lipid peroxidation by measuring malondialdehyde formed as well as by accompanying oxygen uptake were demonstrated in the mitochondria-like particles. A lipid quinone, possibly with a short side chain and related to ubiquinone, was detected in the worms. The results suggested the existence of two cyanide-insensitive oxygen-consuming reactions in Setaria: one respiratory substrate-independent lipid peroxidation, and a second substrate-dependent reaction that requires an auto-oxidizable quinone but not a cytochrome system.

Animals↗
PubMed1988

Occurrence of lipid peroxidation in brain microsomes in the presence of NADH and vanadate.

Oxidation of NADH by rat brain microsomes was stimulated severalfold on addition of vanadate. During the reaction, vanadate was reduced, oxygen was consumed, and H2O2 was generated with a stoichiometry of 1:1 for NADH/O2, as in the case of other membranes. Extra oxygen was found to be consumed over that needed for H2O2 generation specifically when brain microsomes were used. This appears to be due to the peroxidation of lipids known to be accompanied by a large consumption of oxygen. Occurrence of lipid peroxidation in brain microsomes in the presence of NADH and vanadate has been demonstrated. This activity was obtained specifically with the polymeric form of vanadate and with NADH, and was inhibited by the divalent cations Cu2+, Mn2+, and Ca2+, by dihydroxyphenolic compounds, and by hemin in a concentration-dependent fashion. In the presence of a small concentration of vanadate, addition of an increasing concentration of Fe2+ gave increasing lipid peroxidation. After undergoing lipid peroxidation in the presence of NADH and vanadate, the binding of quinuclidinyl benzylate, a muscarinic antagonist, to brain membranes was decreased.

Animals↗
PubMed1988

Vanadate-stimulated NADH oxidation requires polymeric vanadate, phosphate and superoxide.

NADH oxidation, catalyzed by the microsomal enzyme system is stimulated on addition of polymeric vanadate. Maximum stimulation by polymeric vanadate was obtained in the presence of phosphate buffer. The small stimulation obtained by metavanadate (500 microM) increased on acidification followed by neutralization, or on adding a trace amount of polymeric vanadate (1 microM).

Animals↗
PubMed1987

Hypocholesterolemic action of 1-ethoxysilatrane.

Intraperitoneal administration of the organosilicon compound 1-ethoxysilatrane to the rat caused a 25% decrease in the concentration of cholesterol in serum without affecting that of triacylglycerols. The specific activity of 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, was depressed in hepatic microsomes of silatrane-treated animals.

Animals↗