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PubMed1985

Pharmacodynamics of the hypnotic effect of salicylamide in rats.

Salicylamide (SAM) can produce sedation and sleep in humans and animals. To explore the potential utility of the drug as a research tool for assessing disease effects on the response of the central nervous system to depressant drugs, and to obtain a better understanding of the clinically evident sedative action of SAM, studies were performed to characterize the relationship between the concentrations and hypnotic effect of this drug in rats. Female Lewis rats weighing 170-200 g received SAM by intravenous infusion at a rate of 0.49, 1.22, or 2.47 mg/min until the onset of loss of the righting reflex. This well-defined pharmacological endpoint occurred from 16.7 +/- 2.3 min (fastest infusion rate) to 110 +/- 27 min (slowest infusion rate) after the start of the infusion. SAM concentrations at that time in serum, serum water, brain, and cerebrospinal fluid (CSF) were similar in animals that had received the 1.22- or 2.47-mg/min infusion and lower in animals that were infused at a rate of 0.49 mg/min. The slowest infusion rate group also exhibited increased serum protein binding of the drug. The SAM concentration ratio, CSF-serum water, was essentially unity in all three groups, indicative of rapid equilibration of the drug across the blood-CSF barrier. Gentisamide, the hydroxylated metabolite of SAM, was found in serum, CSF, and brain, but in low concentrations at which this metabolite alone had no hypnotic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Molecular composition and origin of substrate-attached material from normal and virus-transformed cells.

The proteins and polysaccharides which are left adherent to the tissue culture substrate after EGTA-mediated removal of normal, virus-transformed, and revertant mouse cells (so-called SAM, or substrate-attached material), and which have been implicated in the cell-substrate adhesion process, have been characterized by SDS-PAGE and other types of analyses under various conditions of cell growth and attachment. The following components have been identified in SAM: 3 size classes of hyaluronate proteoglycans; glycoprotein Co (the LETS glycoprotein); protein Ca (a myosin-like protein); protein Cb(MW 85,000); protein C1 (MW 56,000, which is apparently not tubulin); protein C2 (actin); proteins C3-C5 (histones) which are artifactually bound to the substrate as a result of EGTA-mediated leaching from the cell; and proteins Cc, Cd, Ce, and Cf. The LETS glycoprotein (Co) and Cd appear in newly-synthesized SAM (which is probably enriched in "footpad" material--"footpads" being focal areas of subsurface membraneous contact with the substrate in greater relative quantities than in the SAM accumulated over a long period of time (which is probably enriched in "footprint" material--remnants of footpads left behind as cells move across the substrate). CO and Cd turn over very rapidly following short radiolabeling periods during chase analysis. The SAM's deposited during a wide variety of cellular attachment and growth conditions contained the same components in similar relative proportions. This may indicate well-controlled and coordinate deposition of a cell "surface" complex involving the hyaluronate proteoglycans, the LETS glycoprotein, actin-containing microfilaments with associated proteins, and a limited number of additional proteins in the substrate adhesion site. Evidence indicates that SAM is the remnant of "footpad" vesicles by which the cell adheres to the substrate and that EGTA treatment weakens the subsurface cytoskeleton, allowing these footpad vesicles to be pinched off from the rest of the cell. Three different models of cell-substrate adhesion are presented and discussed.

Cell Adhesion↗
PubMed2005

Protein interactions with model chromatographic stationary phases constructed using self-assembled monolayers.

Model surfaces representative of chromatographic stationary phases were developed by immobilising an homologous series (C2-C18) of n-alkylthiols, mixed monolayers of C4/C18 and thioalkanes with alcohol, carboxylic acid, amino and sulphonic acid terminal groups onto a flat, silver-coated glass surface using self-assembled monolayer (SAM) chemistry. The processes of adsorption and desorption of serum albumins onto the monolayer surfaces was monitored in real-time using surface plasmon resonance (SPR). Alkyl-terminated SAMs all showed a strong adsorption of bovine serum albumin which was largely independent of alkyl chain length, the ratio of mixed C4/C18 SAMs or the solution pH/ionic strength. The adsorption of human serum albumin to carboxylic and amine terminated SAMs was shown to be predominantly via non-electrostatic interactions (hydrophobic or hydrogen bonding). However, sulphonic acid terminated SAMs showed almost exclusively electrostatic interactions with human serum albumin. This preliminary work using self-assembled monolayer chemistry confirms the usefulness of well characterised SAMs surfaces for investigating protein adsorption and desorption onto/from model chromatography surfaces and gives some guidance for selecting appropriate functionalities to develop better surfaces for chromatography and electrophoresis.

Alkylation↗
PubMedDate not supplied

Immobilization of proteins on self-assembled monolayers.

The immobilization of protein molecules on self-assembled monolayers (SAM) by physical interactions and chemical bonding has been studied using atomic force microscopy (AFM). The proteins used for our investigation are bovine serum albumin (BSA), lysozyme (LYZ), and normal rabbit immunoglobulin G (IgG). The surfaces are methyl-, hydroxyl-, carboxylic acid- and aldehyde-terminated SAMs. We found that BSA and LYZ can be readily immobilized on SAMs at their isoelectric point (IEP). The detailed surface morphology of adsorbed proteins varies with the functionality of the SAMs. The strong hydrophobic interaction at the IEP is attributed to immobilization. If the solution pH is deviated from the IEP, proteins may be attached onto the surface via electrostatic interactions. Covalent binding between the aldehyde-terminated SAM and the H2N-groups in the protein results in immobilization of all three proteins. The individual proteins and their orientations on SAMs are clearly resolved from high-resolution AFM images. The stability and bioactivity of these immobilized proteins are also studied.

Adsorption↗
PubMed2000

Movement-related desynchronization of the cerebral cortex studied with spatially filtered magnetoencephalography.

Event-related desynchronization (ERD) within the alpha and beta bands on unilateral index finger extension and hand grasping was investigated on six normal volunteers with magnetoencephalography (MEG). A novel spatial filtering technique for imaging cortical source power, synthetic aperture magnetometry (SAM), was employed for the tomographic demonstration of ERD. SAM source image results were transformed into statistical parametric images. On the same hand grasping task, a functional MRI (fMRI) study was conducted on two subjects and compared with the ERD result. When the MEG data were analyzed with the fast Fourier transformation, power attenuation within the alpha and beta bands was evident on the contralateral sensorimotor area just prior to movement onset. The tomographic distribution of ERD was clearly obtained with SAM statistical imaging analysis. The equivalent current dipole (ECD) for the signal-averaged motor field was localized to the hemisphere contralateral to the hand movement, roughly at the center of the region displaying beta-band ERD. The signal increase on fMRI roughly colocalized with the ERD on the contralateral sensorimotor area. In conclusion, with the novel spatial filtering technique for the brain magnetic field, SAM, cortical regions contributing to ERD on finger movement were successfully demonstrated in a tomographic manner. The relative colocalization of the contralateral SAM ERD with ECD as well as the fMRI activation suggests that SAM is a practically useful technique to extract event-related signals from brain noise.

Adult↗
PubMed1986

Simplified enzymatic synthesis and biodistribution of 11C-S-adenosyl-L-methionine.

11C-S-Adenosyl-L-methionine (11C-SAM) was synthesized enzymatically from 11C-L-methionine using rat-liver extract [40%-50% saturated (NH4)2SO4 fraction] as the enzyme source. In biodistribution studies in rats, the highest uptake of 11C-SAM was found in the kidneys. 11C-SAM was also accumulated in the small intestine, pancreas, adrenal gland, liver, and spleen. The uptake of 11C-SAM in the brain increased with time, but remained low. At 30 min after injection, about 50%-60% of the 11C radioactivity was present in the acid-insoluble fraction of the kidneys and liver. When a high loading dose of 11C-SAM was administered, the kidney uptake was enhanced, but the proportion of the radioactivity present in the acid-insoluble fraction was lower. In a study of one rabbit, the kidney uptake was of 11-SAM clearly visualized using positron-emission tomography.

Animals↗
PubMed1976

Macromolecule synthesis in a mutant of Saccharomyces cerevisiae inhibited by S-adenosyimethionine.

Saccharomyces cerevisiae strain 83384-B3 carries the sai-1 mutation which confers sensitivity to S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH). It was shown that the mutant is impermeable to precursors of ribonucleic acid (RNA) and protein during inhibition by SAM (0.2 mM). Inhibition of uptake of adenine and uracil was nearly complete 3 h after growth in the presence of SAM and the uptake of leucine was at least 10-fold lower. The incorporation of 3H-adenine into ribosomal RNA, transfer RNA and heterodisperse RNA, believed to be messenger, was reduced 10-fold when measured after 1 h inhibition. The inhibition of growth was completely reversed by methionine (2.0 mM) in cells previously exposed to SAM for 90 min. The polysome content in cells inhibited by SAM was 25% less than the control after 4 h inhibition. Ribosome synthesis increased only about 40% in the presence of SAM and about 5-fold in the control over an 8 h period. All classes of RNA were synthesized during inhibition.

Electrophoresis, Polyacrylamide Gel↗
PubMed1993

The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance.

L-dopa, the major treatment for Parkinson's disease (PD), depletes S-adenosyl-L-methionine (SAM). Since SAM causes PD-like symptoms in rodents, the decreased efficacy of chronic L-dopa administered to PD patients may result from a rebound increase in SAM via methionine adenosyl transferase (MAT), which produces SAM from methionine and ATP. This was tested by administering intraperitoneally saline, or L-dopa to mice and assaying for brain MAT activity. As compared to controls, L-dopa (100 mg/kg) treatments of 1 and 2 times per day for 4 days did not significantly increase MAT activity. However, treatments of 3 times per day for 4 and 8 days did significantly increase the activity of MAT by 21.38% and 28.37%, respectively. These results show that short interval, chronic L-dopa treatments significantly increases MAT activity, which increases the production of SAM. SAM may physiologically antagonize the effects of L-dopa and biochemically decrease the concentrations of L-dopa and dopamine. Thus, an increase in MAT may be related to the decreased efficacy of chronic L-dopa therapy in PD.

Adenosine Triphosphate↗
PubMed2002

[Meta-analysis of the efficacy of adenosylmethionine and oxaceprol in the treatment of osteoarthritis].

The aim of this meta-analysis based on the literature was to gather all evidence of randomized clinical trials to assess the efficacy of adenosylmethionine (SAM) and oxaceprol in the treatment of osteoarthritis. Findings in MEDLINE and EMBASE were added to publications catalogued by the AkdA and a reference search. The meta-analysis was based mostly on pain scores but also on pain and function scores. We used the fixed effects and the random effects model.A superiority of SAM vs placebo ( n=468) could not be shown; the 95% CI of standardized difference of pain scores was (-0.89, 0.12). The comparison of SAM vs NSAIDs with seven studies ( n=850) did not show a difference: (-0.59, 0.19). This cannot be seen as proof for equivalence. A post-hoc analysis of SAM vs ibuprofen gave nearly a positive result for SAM: (-0.43, 0.02). No adequate placebo-controlled RCT was found. There was no significance for a difference between oxaceprol and NSAIDs using the four trials found (two diclofenac and two ibuprofen); the 95% CI of standardized difference of pain and function scores was (-0.19, 0.27). Since only a few trials with heterogeneous results were found which mostly have a low quality of the studies and/or publications, the results must be interpreted very carefully. The meta-analysis does not give enough evidence for the efficacy of SAM and oxaceprol for treating the symptoms of osteoarthritis, but it might be that there is a comparable effect to other NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Mechanisms of selenium methylation and toxicity in mice treated with selenocystine.

Mechanisms of selenium methylation and toxicity were investigated in the liver of ICR male mice treated with selenocystine. To elucidate the selenium methylation mechanism, animals received a single oral administration of selenocystine (Se-Cys; 5, 10, 20, 30, 40, or 50 mg/kg). In the liver, both accumulation of total selenium and production of trimethylselenonium (TMSe) as the end-product of methylation were increased by the dose of Se-Cys. A negative correlation was found between production of TMSe and level of S-adenosylmethionine (SAM) as methyl donor. The relationship between Se-Cys toxicity and selenium methylation was determined by giving mice repeated oral administration of Se-Cys (10 or 20 mg/kg) for 10 days. The animals exposed only to the high dose showed a significant rise of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in plasma. Urinary total selenium increased with Se-Cys dose. TMSe content in urine represented 85% of total selenium at the low dose and 25% at the high dose. The potential of Se-methylation and activity of methionine adenosyltransferase, the enzyme responsible for SAM synthesis, and the level of SAM in the liver were determined. The high dose resulted in inactivation of Se-methylation and decrease in SAM level due to the inhibition of methionine adenosyltransferase activity. To learn whether hepatic toxicity is induced by depressing selenium methylation ability, mice were injected intraperitoneally with periodate-oxidized adenosine (100 mumol/kg), a known potent inhibitor of the SAM-dependent methyltransferase, at 30 min before oral treatment of Se-Cys (10, 20, of 50 mg/kg). Liver toxicity induced by selenocystine was enhanced by inhibition of selenium methylation. These results suggest that TMSe was produced by SAM-dependent methyltransferases, which are identical with those involved in the methylation of inorganic selenium compounds such as selenite, in the liver of mice orally administered Se-Cys. Depression of selenium methylation ability resulting from inactivation of methionine adenosyltransferase and Se-methylation via enzymic reaction was also found in mice following repeated oral administration of a toxic dose of Se-Cys. The excess selenides accumulating during the depression of selenium methylation ability may be involved in the liver toxicity caused by Se-Cys.

Adenosine↗
PubMed2006

The electrochemical behavior of p-benzenediol on a self-assembled monolayers Pt electrode modified with N-(2-mercapto-1,3,4-thiadiazol-5-yl)-N'-(4-substituted-arylacetyl) urea.

Two novel N-(2-mercapto-1,3,4-thiadiazol-5-yl)-N'-(4-substituted-arylacetyl) urea compounds have been synthesized, characterized by NMR and MS, and used as self-assembly reagents to form self-assembled monolayers (SAMs) on Pt electrodes. The modified electrodes were characterized by electrochemical methods. The electrochemical behavior of p-benzenediol at the SAMs electrodes was investigated. It was found that the electrochemical response to p-benzenediol is controlled by diffusion and can be electrocatalyzed to obtain more symmetrical redox peaks and higher voltammetric current response at the SAMs electrodes, with a peak separation of 80 mV. For p-benzenediol the process at the SAMs electrodes is quasi-reversible with a rate constant of 0.6742 s-1. The SAMs electrodes have been used to determine p-benzenediol by differential pulse voltammetry. The peak current was linear for concentrations of p-benzenediol in the range 1x10(-7)-5x10(-4) mol L-1 and the detection limit was 4.0x10(-8) mol L-1. The SAMs electrodes were used to determine p-benzenediol in real photographic developer and in a synthetic waste water sample; the standard addition recovery was in the range 96.6-100.4%.

Electrochemistry↗
PubMed2004

Salt stress enhances xylem development and expression of S-adenosyl-L-methionine synthase in lignifying tissues of tomato plants.

S-Adenosyl-L-methionine synthase (SAM; ATP: L-methionine adenosyltransferase, EC 2.5.1.6) catalyzes the biosynthesis of S-adenosyl-L-methionine (AdoMet), a universal methyl-group donor. This enzyme is induced by salinity stress in tomato (Lycopersicon esculentum Mill.). To elucidate the role of SAM and AdoMet in the adaptation of plants to a saline environment, the expression pattern and histological distribution of SAM was investigated in control and salt-stressed tomato plants. Immunohistochemical analysis showed that SAM proteins were expressed in all cell types and plant organs, albeit with preferential accumulation in lignified tissues. Lignin deposition was estimated by histochemical tests and the extent of tissue lignification in response to salinity was quantified by image analysis. The average number of lignified cells in vascular bundles was significantly greater in plants under salt stress, with a maximal expansion of the lignified area found in the root vasculature. Accordingly, the greatest abundance of SAM gene transcripts and proteins occurred in roots. These results indicate that increased SAM activity correlated with a greater deposition of lignin in the vascular tissues of plants under salinity stress. A model is proposed in which an increased number of lignified tracheary elements in tomato roots under salt stress may enhance the cell-to-cell pathway for water transport, which would impart greater selectivity and reduced ion uptake, and compensate for diminished bulk flow of water and solutes along the apoplastic pathway.

Environment↗
PubMed2005

Immunohistochemical localization of IAA and ABP1 in strawberry shoot apexes during floral induction.

By using an anti-indole-acetic acid (anti-IAA) monoclonal antibody and an anti-auxin-binding protein 1 (anti-ABP1) polyclonal antibody, IAA and ABP1 were immunohistochemically localized in strawberry (Fragaria ananassa Duch.) shoot apexes during floral induction. The spatial distribution patterns of endogenous IAA and ABP1 and their dynamic changes during floral induction were investigated. In addition, the affect of 1-N-naphthylphtalamic acid (NPA) on IAA distribution during floral induction was also analyzed. The results showed that IAA was present in the shoot apexes throughout the floral induction process, gradually concentrating in the shoot apical meristem (SAM). The distribution of ABP1 and its dynamic changes were similar to those of IAA. In addition, the ABP1 immune signal in SAM gradually increased as floral induction developed. On a morphological level, these results indicate both the spatial distribution and dynamic changes in endogenous IAA and ABP1 during the floral induction process. The close correlation found between IAA and ABP1 indicates that a cooperation occurs during the regulation of floral induction. The results also suggest that IAA was the significant agent for floral induction, and that SAM might be the place of the main action. Treatment with NPA during floral induction prevented the accumulation of IAA in the SAM, delayed the process of floral differentiation and induced an abnormal flower development. It is likely that IAA in the shoot apex is produced in young leaves and transported through the vascular tissues to the SAM and other places of function. Finally, an appropriate amount of IAA in the SAM and normal polar auxin transport are essential for floral induction and differentiation in strawberries.

Cell Differentiation↗
PubMed2005

Pattern formation in the monocot embryo as revealed by NAM and CUC3 orthologues from Zea mays L.

All aerial parts of a higher plant originate from the shoot apical meristem (SAM), which is initiated during embryogenesis as a part of the basic body plan. In contrast to dicot species, the SAM in Zea mays is not established at an apico-central, but at a lateral position of the transition stage embryo. Genetic and molecular studies in dicots have revealed that members of the NAC gene family of plant-specific transcription factors such as NO APICAL MERISTEM (NAM) from Petunia or the CUP-SHAPED COTYLEDON (CUC) genes from Arabidopsis contribute essential functions to the establishment of the SAM and cotyledon separation. As an approach to the understanding of meristem formation in a monocot species, members of the maize NAC family highly related to the NAM/CUC genes were isolated and characterized. Our phylogenetic analysis indicates that two distinct NAM and CUC3 precursors already existed prior to the separation of mono- and dicot species. The allocation of the two maize paralogues, ZmNAM1 and ZmNAM2 together with PhNAM, AtCUC2 and AmCUP in one sub-branch and the corresponding expression patterns support their contribution to SAM establishment. In contrast, the ZmCUC3 orthologue is associated with boundary specification at the SAM periphery, where it visualizes which fraction of cells in the SAM is committed to a new leaf primordium. Other maize NAC gene family members are clearly positioned outside of this NAM/CUC3 branch and also exhibit highly cell type-specific expression patterns.

Amino Acid Sequence↗
PubMed1989

Effects of indeloxazine hydrochloride on passive avoidance behavior of senescence-accelerated mice.

The effects of indeloxazine hydrochloride on disturbances of passive avoidance behavior in senescence-accelerated mice (SAM) were observed. The step-through latency of SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) was significantly shorter than that of SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain). The administration of indeloxazine (10-30 mg/kg p.o.) or dihydroergotoxine (1 mg/kg i.p.) for 3 weeks significantly prolonged the step-through latency of SAM-P/8/Ta whereas piracetam (30-300 mg/kg p.o.) did not. These results suggest that indeloxazine has a facilitatory effect on cerebral functions and that it has a broader pharmacological profile in anti-amnesic activities than piracetam.

Aging↗
PubMed1989

Regulation of S-adenosyl methionine synthesis in the mouse embryo.

In early embryos, methylation is involved in "gamete imprinting" and inactivation of artificially introduced foreign genes. We studied the biosynthesis of the universal methylation cofactor: S-Adenosyl methionine (SAM). In the mouse, SAM conversion from methionine is limited by saturation of the methionine endogenous pool. SAM is present at a practically unchanged level from the unfertilized oocyte to early morula. SAM synthesis is increased at the time of compaction. In blastocysts, although methionine uptake is increased, the conversion rate from methionine is lowered. We observed no differences between C57 Black and Swiss albino random bred strains. In few experiments with human unfertilized oocytes and spared embryos, we observed higher methionine incorporation, and higher conversion to SAM. Next, the effect of two methylation inhibitors was tested, on early mouse embryonic development, at the one-cell and the two-cell stage. We found that ethionine is very toxic, even at the lowest tested concentration of 25 microM. Homocysteine is more potent at the one-cell stage than at the 2-cell stage, and it only partially blocks blastocyst formation from the 2-cell stage even at a concentration of 500 microM. It clearly acts as a methylation inhibitor; it lowers the SAM pool and the methylation index, SAH/SAM ratio (SAH: S-Adenosyl Homocysteine). We also found that homocysteine is an unexpected competitor for methionine influx and efflux.

Animals↗
PubMed1988

Postnatal changes in lung phospholipids and alveolar macrophages in term newborn monkeys.

In order to better understand the postnatal sequence of surfactant secretion and establishment of the alveolar macrophage (AM) population in newborn primates, healthy Macaca nemestrina monkeys were sacrificed during fetal life at term gestation (n = 5), or at 2 days (n = 5) or 3-4 weeks (n = 5) after term vaginal delivery. Excised lung tissue and left lung lavage were analyzed for phospholipid (PL) content, surface active material (SAM) extract, PL components, surface activity, pressure-volume characteristics, and AM number. Compared to term fetal animals, 2 day old term newborn monkeys were found to have a several-fold increase in lavage PL and SAM, and this was associated with greater maximal lung volume and drier lungs, but not improved deflation stability. During the subsequent 3-4 weeks of life, a 42% reduction in lung tissue stores of PL and SAM, and an 87% reduction in lavage PL and SAM were noted. Despite these major changes in quantity, there were relatively minor changes in the composition of the PL synthesized and released. The reduced quantity of SAM in the 3-4 week old animals led to a small decline in deflation stability. The several-fold increase in lavage PL and SAM during the first 2 days of life was accompanied by a 33-fold increase in AM; there was an additional 4-fold increase in AM number by 3-4 weeks of age. The abundance of lavage surfactant at 2 days of age may play a role in the influx of AM.

Animals↗
PubMed1989

Inhibition by ethanol of rat liver plasma membrane (Na+,K+)ATPase: protective effect of S-adenosyl-L-methionine, L-methionine, and N-acetylcysteine.

(Na+,K+)ATPase activity of rat liver plasma membranes was evaluated in female rats feeding an ethanol containing diet for 46 days (total ethanol ingested, 59.7 g/100 g body wt). Determinations were performed at the end of ethanol treatment or at various times after stopping treatment. (Na+,K+)ATPase and 5'-nucleotidase activities exhibited a 8- and 1.4-fold decrease, respectively, at the end of ethanol ingestion. In contrast no modifications of Mg2+-ATPase activity were observed. There also occurred, in ethanol-treated rats, release of sorbitol dehydrogenase into the blood, fat accumulation in liver cells, and decrease in reduced glutathione (GSH) liver content. A decrease in (Na+,K+)ATPase activity was also found in plasma membranes isolated from hepatocyte suspensions after a 2-hr incubation with 50 mM ethanol or 1 mM acetaldehyde (ACA), in conditions that caused a great fall in hepatocyte GSH content but did not cause cell death. After the cessation of ethanol administration, there occurred a progressive recovery of (Na+,K+)ATPase activity, GSH and triacylglycerol content, and release of sorbitol dehydrogenase. These parameters reached control values 12 hr after ethanol withdrawal. S-Adenosyl-L-methionine (SAM), L-methionine, and N-acetylcysteine (NAC), given to rats during ethanol treatment, prevented the decrease in (Na+,K+)ATPase activity and GSH content. They also reduced steatosis and liver necrosis. The efficiency of these compounds decreased in this order: SAM, methionine, NAC. SAM accelerated the recovery of all parameters studied after ethanol withdrawal, and also protected (Na+,K+)ATPase activity and GSH content of isolated hepatocytes from the deleterious effect of ethanol. These SAM effects were prevented by 1-chloro-2,4-dinitro-benzene, a compound which depletes cell GSH. Treatment of isolated hepatocytes with [35S]SAM led to the synthesis of labeled GSH. The total amount and specific activity of labeled GSH underwent a significant increase, in the presence of 2 mM ethanol or 0.5 mM ACA, which indicates a marked stimulation of GSH synthesis by ethanol and ACA. These data indicate that ethanol intoxication may inhibit (Na+,K+)ATPase activity; an effect that does not seem to depend on cell necrosis. SAM, methionine, and NAC exert various degrees of protection toward ethanol-induced cell injury, which are related to the efficiency of these compounds in maintaining a high GSH pool.

Acetaldehyde↗