scholarly journals Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters

1997 ◽  
Vol 78 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Fabio Favilli ◽  
Patrizia Marraccini ◽  
Teresa Iantomasi ◽  
Maria T. Vincenzini
Keyword(s):  
Amino Acids ◽  
Oral Administration ◽  
Degradation Products ◽  
Specific Inhibitor ◽  
Buthionine Sulfoximine ◽  
Transport Systems ◽  
Rat Jejunum ◽  
Equivalent Amount ◽  
Specific Transport

The present study reports data on absorption of orally administered glutathione (GSH) in rat jejunum and in other organs, and the possible role of specific transport systems of GSH and γ-glutamyltranspeptidase (EC 2.3.2.1; γ-GT) activity. GSH levels were measured simultaneously in various organs after oral GSH administration to untreated rats and rats treated with L-buthionine sulfoximine (BSO) or acivicin (AT125). BSO selectively inhibits GSH intracellular synthesis and AT125 is a specific inhibitor of γ-GT activity. GSH levels were also measured after oral administration of an equivalent amount of the constituent amino acids of GSH to untreated and BSO-treated rats. Significant increases in GSH levels were found in jejunum, lung, heart, liver and brain after oral GSH administration to untreated rats. GSH increases were also obtained in all organs, except liver, when GSH was administered to rats previously GHS-depleted by treatment with BSO. The analysis of all results allowed us to distinguish between the increase in GSH intracellular levels due to intact GSH uptake by specific transporters, and that due to GSH degradation by γ-GT activity and subsequent absorption of degradation products with intracellular resynthesis of GSH; both these mechanisms seemed to be involved in increasing GSH content in heart after oral GSH administration. Jejunum, lung and brain took up GSH mostly intact, by specific transport systems, while in liver GSH uptake occurred only by its breakdown by γ-GT activity followed by intracellular resynthesis.

Lysosomal-type PLA2and turnover of alveolar DPPC

2001 ◽  
Vol 280 (4) ◽  
pp. L748-L754 ◽  
Author(s):  
Aron B. Fisher ◽  
Chandra Dodia
Keyword(s):  
Degradation Products ◽  
Specific Inhibitor ◽  
Rat Lung ◽  
Lamellar Bodies ◽  
Lung Uptake ◽  
Rat Lungs ◽  
Choline Incorporation ◽  
Total Tissue ◽  
Intact Rats

This study evaluated the role of a lysosomal-type phospholipase A2(aiPLA2) in the degradation of internalized dipalmitoylphosphatidylcholine (DPPC) and in phospholipid synthesis by the rat lung. Uptake and degradation of DPPC were measured in isolated perfused rat lungs over 3 h following endotracheal instillation of [3H]DPPC in mixed unilamellar liposomes plus or minus MJ33, a specific inhibitor of lung aiPLA2. Uptake of DPPC was calculated from total tissue-associated radiolabel, and degradation was calculated from the sum of radiolabel in degradation products. Both uptake and degradation were markedly stimulated by addition of 8-bromo-cAMP to the perfusate. MJ33 had no effect on DPPC uptake but decreased DPPC degradation at 3 h by ∼40–50%. The effect of MJ33 on lung synthesis of DPPC was evaluated with intact rats over a 12- to 24-h period following intravenous injection of radiolabeled palmitate and choline. MJ33 treatment decreased palmitate incorporation into disaturated phosphatidylcholine of lamellar bodies and surfactant by ∼65% at 24 h but had no effect on choline incorporation. This result is compatible with inhibition of the deacylation/reacylation pathway for DPPC synthesis. These results obtained with intact rat lungs indicate that aiPLA2is a major enzyme for degradation of internalized DPPC and also has an important role in DPPC synthesis.

scholarly journals Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes

2005 ◽  
Vol 49 (5) ◽  
pp. 1988-1993 ◽  
Author(s):  
Karima El Fadili ◽  
Nadine Messier ◽  
Philippe Leprohon ◽  
Gaétan Roy ◽  
Chantal Guimond ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Leishmania Infantum ◽  
Dna Microarrays ◽  
Specific Inhibitor ◽  
Buthionine Sulfoximine ◽  
Protozoan Parasite ◽  
Sodium Stibogluconate ◽  
Glutathione Biosynthesis ◽  
Antimony Resistance

ABSTRACT Antimonial compounds are the mainstay for the treatment of infections with the protozoan parasite Leishmania. We present our studies on Leishmania infantum amastigote parasites selected for resistance to potassium antimonyl tartrate [Sb(III)]. Inside macrophages, the Sb(III)-selected cells are cross-resistant to sodium stibogluconate (Pentostam), the main drug used against Leishmania. Putative alterations in the level of expression of more than 40 genes were compared between susceptible and resistant axenic amastigotes using customized DNA microarrays. The expression of three genes coding for the ABC transporter MRPA (PGPA), S-adenosylhomocysteine hydrolase, and folylpolyglutamate synthase was found to be consistently increased. The levels of cysteine were found to be increased in the mutant. Transfection of the MRPA gene was shown to confer sodium stibogluconate resistance in intracellular parasites. This MRPA-mediated resistance could be reverted by using the glutathione biosynthesis-specific inhibitor buthionine sulfoximine. These results highlight for the first time the role of MRPA in antimony resistance in the amastigote stage of the parasite and suggest a strategy for reversing resistance.

Role of transglutaminase and protein cross-linking in the repair of mucosal stress erosions

1992 ◽  
Vol 262 (5) ◽  
pp. G818-G825 ◽  
Author(s):  
J. Y. Wang ◽  
L. R. Johnson
Keyword(s):  
Enzyme Activity ◽  
Oral Administration ◽  
Specific Inhibitor ◽  
Duodenal Mucosa ◽  
Mucosal Healing ◽  
Cross Linking ◽  
Xiphoid Process ◽  
Transglutaminase Activity ◽  
Protein Cross Linking

We have recently demonstrated that polyamines are absolutely required for gastric and duodenal mucosal repair after stress. Polyamines act as substrates for transglutaminase and facilitate protein cross-linking. The current study tests whether transglutaminase and protein cross-linking are involved in the mechanism of mucosal healing. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 6 h. Animals were killed immediately or 4, 12, or 24 h after stress. Gastric and duodenal mucosa were examined histologically and grossly, and transglutaminase activity was measured. Transglutaminase activity in gastric and duodenal mucosa was increased significantly from 0 to 8 h, peaking 4 h after the 6-h stress period. By 12 h, enzyme activity in duodenal mucosa had returned to control values while gastric mucosal transglutaminase did not decrease to control values until 24 h. Mucosal recovery from lesions produced by stress was evident 12 h after stress and was almost complete by 24 h. Dansylcadaverine (100 mg/kg, orally), a specific inhibitor of protein cross-linking, not only prevented the increases in transglutaminase but significantly decreased healing in both tissues. Oral administration of the polyamine spermidine (100 mg/kg) immediately after stress totally prevented inhibition of repair caused by blocking ornithine decarboxylase with difluoromethylornithine (DFMO, 500 mg/kg). Administration of dansylcadaverine, together with spermidine, significantly prevented the beneficial effect of spermidine on mucosal healing in the DFMO-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cellular aspects of folate and antifolate membrane transport.

2000 ◽  
Vol 47 (3) ◽  
pp. 735-749 ◽  
Author(s):  
A Brzezińska ◽  
P Wińska ◽  
M Balińska
Keyword(s):  
Amino Acids ◽  
Membrane Transport ◽  
Physiological Role ◽  
Cancer Development ◽  
Transport Systems ◽  
Transport Activity ◽  
Neoplastic Cells ◽  
Folate Receptors

Folates--one carbon carriers--take part in the metabolism of purine, thymidylate and some amino acids. Internalization of these compounds employs several mechanisms of transport systems. Reduced folate carriers and folate receptors play the most important role in this process. The physiological role of these molecules in normal and neoplastic cells is described regarding changes in transport activity and connection of transport systems with resistance to antifolates and cancer development.

Ontogenesis of intestinal taurine transport: evidence for a beta-carrier in developing rat jejunum

1988 ◽  
Vol 254 (6) ◽  
pp. G870-G877 ◽  
Author(s):  
M. S. Moyer ◽  
A. L. Goodrich ◽  
M. M. Rolfes ◽  
F. J. Suchy
Keyword(s):  
Amino Acids ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Equilibrium Concentration ◽  
Membrane Vesicles ◽  
Transport Systems ◽  
Rat Jejunum ◽  
Adult Rats ◽  
Taurine Transport ◽  
Taurine Uptake

Taurine, a sulfur-containing beta-amino acid, may be conditionally essential during development. However, the existence of a carrier system for beta-amino acids has not been demonstrated in brush-border membrane vesicles (BBMV) from adult rat jejunum. We studied the uptake of [3H]taurine in BBMV prepared from the jejunum of developing and adult rats using a cation-precipitation technique. Uptake of 10 microM [3H]taurine by adult BBMV was slightly enhanced in the presence of an inwardly directed 100 mM Na+ gradient compared with a K+ gradient, and there was no intravesicular accumulation of isotope above the equilibrium concentration ("overshoot"). In contrast, taurine transport by BBMV from 10-day-old rat pups was markedly accelerated in the presence of a Na+ gradient compared with a K+ gradient and a twofold overshoot was observed. Na+-dependent taurine uptake was inhibited by the structural analogues hypotaurine and beta-alanine but not by alpha-alanine or glutamine, which are amino acids served by other transport systems. By computer analysis, Na+-dependent taurine uptake (2-1,000 microM) was saturable with an apparent Km of 74.80 +/- 11.87 microM and a Vmax of 53.55 +/- 2.76 pmol.mg protein-1.min-1. With increasing postnatal age, there was a marked decrease in the initial rate and peak intravesicular accumulation of taurine with disappearance of the overshoot by 21 days of age. We conclude 1) a Na+-dependent carrier mechanism for taurine transport is present in the brush-border membrane of suckling rat jejunum and 2) the activity of this carrier decreases after weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

Two cationic amino acid transport systems in human placental basal plasma membranes

1991 ◽  
Vol 261 (2) ◽  
pp. C246-C252 ◽  
Author(s):  
T. C. Furesz ◽  
A. J. Moe ◽  
C. H. Smith
Keyword(s):  
Amino Acids ◽  
Time Course ◽  
Plasma Membranes ◽  
Membrane Vesicles ◽  
Basal Membrane ◽  
Transport Systems ◽  
Cationic Amino Acid ◽  
Basal Plasma ◽  
Cationic Amino Acids

Transport of cationic amino acids in basal (fetal facing) plasma membranes was investigated by characterization of L-[3H]lysine and L-[3H]arginine uptake in membrane vesicles isolated from term human placentas. At least two Na(+)-independent systems were present. Lysine concentration dependence data were fit by a two-system model with Km values of 1.0 +/- 0.8 and 223 +/- 57 microM and Vmax values of 0.06 +/- 0.03 and 24.0 +/- 5.8 pmol.mg protein-1.min-1. In the presence of either 10 mM L-leucine or Na+ plus 10 mM L-homoserine, the data were fit by single system models with kinetic parameters similar to the higher and lower Km systems seen in the absence of inhibitors. Uptake of 10 or 20 microM L-lysine in the absence of Na+ showed the higher Km system was inhibited completely by L-arginine, L-homoarginine, and L-histidine. In the presence of Na+, the higher Km system was inhibited completely by L-alanine, L-homoserine, L-leucine, L-phenylalanine, and L-norleucine. The lower Km system was inhibited completely by L-arginine, L-homoarginine, L-histidine, L-leucine, and L-methionine. Time course studies of uptake demonstrated that uptake by either system alone filled the total vesicular space. The basal membrane of human placental syncytiotrophoblast possesses two transport systems for lysine and arginine, resembling the ubiquitous y+ system and the bo,+ system previously described in mouse blastocysts. The higher Vmax of the y+ system suggests that in utero it may mediate transfer of cationic amino acids from the syncytiotrophoblast to the fetus. The role of the high-affinity low-capacity bo,+ system remains to be determined.

scholarly journals Integrative Study Supports the Role of Trehalose in Carbon Transfer From Fungi to Mycotrophic Orchid

2021 ◽  
Vol 12 ◽  
Author(s):  
Jan Ponert ◽  
Jan Šoch ◽  
Stanislav Vosolsobě ◽  
Klára Čiháková ◽  
Helena Lipavská
Keyword(s):  
Amino Acids ◽  
High Performance ◽  
Specific Inhibitor ◽  
Soluble Carbohydrates ◽  
Mycorrhizal Symbiosis ◽  
Trehalase Activity ◽  
Carbon Transfer ◽  
Integrative Study ◽  
The Common

Orchids rely on mycorrhizal symbiosis, especially in the stage of mycoheterotrophic protocorms, which depend on carbon and energy supply from fungi. The transfer of carbon from fungi to orchids is well-documented, but the identity of compounds ensuring this transfer remains elusive. Some evidence has been obtained for the role of amino acids, but there is also vague and neglected evidence for the role of soluble carbohydrates, probably trehalose, which is an abundant fungal carbohydrate. We therefore focused on the possible role of trehalose in carbon and energy transfer. We investigated the common marsh orchid (Dactylorhiza majalis) and its symbiotic fungus Ceratobasidium sp. using a combination of cultivation approaches, high-performance liquid chromatography, application of a specific inhibitor of the enzyme trehalase, and histochemical localization of trehalase activity. We found that axenically grown orchid protocorms possess an efficient, trehalase-dependent, metabolic pathway for utilizing exogenous trehalose, which can be as good a source of carbon and energy as their major endogenous soluble carbohydrates. This is in contrast to non-orchid plants that cannot utilize trehalose to such an extent. In symbiotically grown protocorms and roots of adult orchids, trehalase activity was tightly colocalized with mycorrhizal structures indicating its pronounced role in the mycorrhizal interface. Inhibition of trehalase activity arrested the growth of both symbiotically grown protocorms and trehalose-supported axenic protocorms. Since trehalose constitutes only an inconsiderable part of the endogenous saccharide spectrum of orchids, degradation of fungal trehalose likely takes place in orchid mycorrhiza. Our results strongly support the neglected view of the fungal trehalose, or the glucose produced by its cleavage as compounds transported from fungi to orchids to ensure carbon and energy flow. Therefore, we suggest that not only amino acids, but also soluble carbohydrates are transported. We may propose that the soluble carbohydrates would be a better source of energy for plant metabolism than amino acids, which is partially supported by our finding of the essential role of trehalase.

scholarly journals Oral and pre-absorptive sensing of amino acids relates to hypothalamic control of food intake in rainbow trout

2020 ◽  
Vol 223 (17) ◽  
pp. jeb221721
Author(s):  
Sara Comesaña ◽  
Marta Conde-Sieira ◽  
Cristina Velasco ◽  
José L. Soengas ◽  
Sofia Morais
Keyword(s):  
Amino Acids ◽  
Rainbow Trout ◽  
Food Intake ◽  
Oral Administration ◽  
Glutamic Acid ◽  
Oral Treatment ◽  
Taste Receptor ◽  
Induced Changes ◽  
First Time

ABSTRACTTo assess the putative role of taste and pre-absorptive sensing of amino acids in food intake control in fish, we carried out an oral administration with l-leucine, l-valine, l-proline or l-glutamic acid in rainbow trout (Oncorhynchus mykiss). Treatment with proline significantly reduced voluntary food intake at 2 h and 3 h after oral administration, while glutamic acid showed a less pronounced satiating effect at 3 h. The mRNA expression of taste receptor subunits tas1r1, tas1r2a, tas1r2b and tas1r3 was measured in the epithelium overlying the bony basihyal of the fish (analogous to the tetrapod tongue) at 10, 20 or 30 min following treatment. No significant changes were observed, except for a tas1r down-regulation by valine at 30 min. Of the downstream taste signalling genes that were analysed in parallel, plcb2 and possibly trpm5 (non-significant trend) were down-regulated 20 min after proline and glutamic acid treatment. The signal originated in the oropharyngeal and/or gastric cavity presumably relays to the brain as changes in genes involved in the regulation of food intake occurred in hypothalamus 10–30 min after oral treatment with amino acids. In particular, proline induced changes consistent with an increased anorexigenic potential in the hypothalamus. We have therefore demonstrated, for the first time in fish, that the peripheral (pre-absorptive) detection of an amino acid (l-proline), presumably by taste-related mechanisms, elicits a satiety signal that in hypothalamus is translated into changes in cellular signalling and neuropeptides regulating food intake, ultimately resulting in decreased food intake.

Modulation of cisplatin chronotoxicity related to reduced glutathione in mice

1996 ◽  
Vol 15 (7) ◽  
pp. 563-572 ◽  
Author(s):  
NA Boughattas ◽  
XM Li ◽  
J. Filipski ◽  
G. Lemaigre ◽  
E. Filipski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Circadian Rhythm ◽  
Reduced Glutathione ◽  
Kidney Tissue ◽  
Specific Inhibitor ◽  
Buthionine Sulfoximine ◽  
Sampling Time ◽  
Important Influence ◽  
Tissue Sampling

Intracellular reduced glutathione (GSH) concentrations were measured according to the tissue sampling-time along the 24 h scale in male B6D2F1 mice. A significant circadian rhythm in GSH content was statistically validated in liver, jejunum, colon and bone-marrow (P≤0.02) but not in kidney. Tissue GSH concentration increased in the dark-activity span and decreased in the light-rest span of mice. The minimum and maximum of tissue GSH content corresponded respectively to the maximum and minimum of cisplatin (CDDP) toxicity. The role of GSH rhythms with regard to CDDP toxicity was investigated, using a specific inhibitor of GSH biosynth esis, buthionine sulfoximine (BSO). Its effects were assessed on both tissue GSH levels and CDDP toxicity at three circadian times. BSO resulted in a 10-fold decrease of the 24 h-mean GSH in kidney. However a moderate GSH decrease characterized liver (-23%) and jejunum (-30%). BSO pretreatment largely enhanced CDDP toxicity which varied according to a circadian rhythm. Although BSO partly and/or totally abolished the tissue GSH rhythms, it did not modify those in CDDP toxicity. We conclude that GSH have an important influence on CDDP toxicity but not in the circadian mechanism of such platinum chronotoxicity.

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