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At least 1,207 records · Page 67Linked to original sources
PubMed1992

Cerebral taurine transport is increased during streptozocin-induced diabetes in rats.

Taurine is a cerebral osmolyte whose intracellular content changes in parallel with plasma osmolality. We conducted experiments to assess whether cerebral taurine transport is modified during chronic hyperglycemia. Rats with STZ-induced diabetes were studied after 1 wk of sustained hyperglycemia. Cerebral taurine uptake in synaptosomes (metabolically active nerve terminal vesicles) was measured using a rapid filtration technique. The synaptosomes were isolated by homogenization of the brain and purification on discontinuous Ficoll gradients (n = 8 synaptosome preparations). Diabetic rats (n = 13) displayed a 15-25% increase in synaptosomal taurine uptake compared with normoglycemic control animals (n = 12) at all time points assayed between 5 and 120 min. Thus, after a 30-min incubation, cerebral taurine uptake increased from a control level of 3.53 +/- 0.23 to 4.10 +/- 0.24 mumol/mg protein (n = 10) in hyperglycemic rats, P less than 0.03. The magnitude of the plasma-to-brain cell taurine gradient was unchanged in diabetic animals. The intrasynaptosomal taurine concentration (approximately 2 microM) and taurine efflux from the synaptosomes were no different in hyperglycemic versus control rats; efflux amounted to less than 2.5% of the uptake value at corresponding time points. Maximal brain taurine uptake under both control and experimental hyperglycemic conditions required the presence of external Na+ and Cl-. Synaptosomal taurine transport was reduced by competing beta-amino acids such as beta-alanine, beta-aminoisobutyric acid, and hypotaurine (P less than 0.01). Addition of oubain and the anionic binding site inhibitors, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid and 4,4'diisothio-cyanatostilbene-2,2'-disulfonic acid, also decreased cerebral taurine uptake under normoglycemic and hyperglycemic conditions (P less than 0.01). The increased synaptosomal taurine uptake by diabetic rats was not a result of generalized membrane dysfunction because glycine transport was not elevated in hyperglycemic rats. The enhanced transport rate was attributable to a 35 and 81% increase in the Vmax of the high- and low-affinity taurine transporters, respectively (P less than 0.01), without significant change in the Km of the carrier systems. Treatment of hyperglycemic rats (n = 5) with ultra-long-acting insulin to normalize the serum glucose concentration restored synaptosomal taurine uptake to the level observed in normoglycemic controls. The effect of insulin was attributable to correction of hyperglycemia, because addition of insulin (500 mU/ml) to the in vitro assay system did not alter synaptosomal taurine uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Mechanism of ketoconazole-induced elevation of individual serum bile acids in the rat: relationship to the effect of ketoconazole on bile acid uptake by isolated hepatocytes.

Ketoconazole, an imidazole derivative, has been implicated in a number of hepatic dysfunctions. The aim of the present study was to determine the effect of in vivo treatment of rats with ketoconazole on individual serum bile acid levels and the in vitro effects of ketoconazole on the hepatocellular uptake of two bile acids and two other model substrates transported by liver cells. Male Sprague-Dawley rats were treated i.p. with a single injection of ketoconazole of 25 mg/kg (n = 4) or 50 mg/kg (n = 4); the control group (n = 4) received the vehicle only at a dose of 1 ml/kg. Blood samples were collected at 4 hr after dosing. With high-performance liquid chromatography, the serum was assayed for individual serum bile acids. At the higher dose, ketoconazole produced a significant increase in serum levels of cholic acid, taurocholic acid, chenodeoxycholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid and taurochenodeoxycholic acid compared with the control group (P < .05). Cholic acid, taurocholic acid and chenodeoxycholic acid levels were significantly raised in rats treated with the lower dose. In vitro, ketoconazole strongly inhibited the hepatocellular uptake of [14C]cholic acid, [14C]taurocholic acid and [3H]ouabain but not [14C]2-aminoisobutyric acid, which indicated that the effect is relatively specific. The kinetics of inhibition were competitive and the inhibition constants for taurocholate and ouabain were 6 and 1 microM, respectively. Ketoconazole inhibited by both Na(+)-dependent taurocholate uptake and stimulated bile acid countertransport of preloaded hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Differential effects of okadaic acid on insulin-stimulated glucose and amino acid uptake and phosphatidylinositol 3-kinase activity.

The effect of okadaic acid, a serine/threonine phosphatase inhibitor, was analyzed in two insulin-responsive systems, the isolated mouse soleus muscle and 3T3-L1 adipocytes. While okadaic acid alone was a potent stimulator of glucose transport in both systems, it prevented transport stimulation by insulin. To gain insight into this inhibitory action, the activation of phosphatidylinositol 3-kinase (PI3-kinase), one of the earliest postreceptor steps identified so far, was studied. In 3T3-L1 adipocytes and muscle, insulin increased PI3-kinase activity in immunoprecipitates obtained with antibodies to phosphotyrosine. Okadaic acid alone had no effect but strongly inhibited this hormonal action. Okadaic acid treatment did not interfere with insulin-induced receptor autophosphorylation or with its tyrosine kinase activity toward artificial substrates. In contrast, in the presence of the phosphatase inhibitor, we did not observe tyrosine phosphorylation of the insulin receptor cellular substrate p185 (IRS-1) or immunoprecipitation of PI3-kinase by antibodies to phosphotyrosine. These results suggest that okadaic acid interferes with insulin's stimulation of glucose transport by inhibiting IRS-1 phosphorylation and its association with PI3-kinase and/or other signaling molecules. However, okadaic acid did not block the insulin stimulation of aminoisobutyric acid uptake in muscle. This would indicate that IRS-1 phosphorylation and PI3-kinase activation are not required for all the effects of insulin and that the serine/threonine phosphorylation events implicated in the translocation of glucose transporters are not controlling amino acid transport in muscle.

3T3 Cells↗
PubMed1988

Regulation of amino acid transport in hepatocytes isolated from adult and old rats.

The 2-aminoisobutyric acid transport in hepatocytes isolated from 3- and 24-month-old rats was studied and some age-related differences were observed. The basal uptake appeared to be almost constant in cells from old animals during the incubation time, while, in the cells from adults, it showed a progressive increase, interpreted as being due to a derepression mechanism. Epinephrine and glucagon increased the transport in hepatocytes from animals of both ages, even if with a slightly different pattern; the hormones increased the Vmax, while the Km was unchanged at each age tested. However, the glucagon-induced increase in Vmax was lower in the older animals. The mechanism of hormonal action appeared to be similar in adult and old rats. In fact the uptake stimulation by glucagon and epinephrine showed a dependence on protein synthesis. The epinephrine effect was mediated by alpha-adrenergic receptors. No effect was exerted by extracellular amino acids on hepatocytes from 24-month-old animals, suggesting a loss of adaptative regulation mechanism with aging. This behaviour was reflected in the kinetic parameters; in fact the Vmax was not modified by extracellular amino acids at 24 months of age, while it appeared to be strongly decreased in the adult.

Aging↗
PubMed1998

Conformation and membrane activity of an analogue of the peptaibol antibiotic trichogin GA IV with a lipophilic amino acid at the N-terminus.

We have synthesized by solution-phase methods two analogues of the 11-residue lipopeptaibol antibiotic trichogin GA IV in which the N-terminal n-octanoyl group is replaced either by an N-acetylated 2-amino-2-methyl-L-undecanoic acid or by an N-acetylated alpha-aminoisobutyric acid. CD, FTIR absorption. and NMR analyses unequivocally show that the main structural features of trichogin GA IV are preserved in these analogues. Since only the peptide containing the lipophilic chain exhibits membrane-modifying properties, these results strongly support the view that moving the long acyl moiety from the Nalpha-blocking group to the side chain of the N-terminal extra-residue does not affect the conformational properties or the membrane activity of trichogin GA IV.

Amino Acid Sequence↗
PubMed1990

Conformationally constrained alpha-helical peptide models for protein ion channels.

Recently we described the design, synthesis, and characterization of some simple amphiphilic alpha-helical models for protein ion channels. These peptides, composed of only Leu and Ser residues, are hypothesized to form helical bundles capable of passing ions across phospholipid bilayers. In an effort to demonstrate that the peptides are, in fact, helical in their active ion-conducting state, the conformationally constrained amino acid, C alpha, C alpha-dimethylglycine (alpha-aminoisobutyric acid, Aib), was introduced simultaneously at three positions into one of the model peptides, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, giving H2N-(Leu-Ser-Leu-Aib-Leu-Ser-Leu)3-CONH2. Examination of a tetrameric model for the channel suggested that this substitution should have a minimal effect on conductance. CD spectroscopy of the Aib-modified and original peptide in phospholipid vesicles indicated that both were highly alpha-helical. Furthermore, the Aib-containing peptide formed proton channels nearly identical in conductance to the original peptide.

Amino Acid Sequence↗
PubMed1978

Amino acid transport in the rat exocrine pancreas. III. Effect of maximal and supramaximal hormonal stimulation in vivo.

Amino acid transport and incorporation have been studied in vitro in rat pancreatic lobules after maximal and supramaximal hormonal stimulation with caerulein. Incorporation into proteins was increased already after 30 and 120 min of maximal stimulation, but was decreased after the infusion of a supramaximal dose. Uptake of neutral amino acids was monitored using labeled leucine and alpha-aminoisobutyric acid (AIB). In the case of leucine the free pool was consistently reduced after maximal stimulation, while supramaximal doses led to an increase which could be potentiated by the addition of 2mM tetracaine. Using AIB, a significant increase in the intracellular pool was observed after maximal stimulation, conversely a decrease after supramaximal stimulation. Release of labeled leucine and AIB from preloaded lobules during incubation in the cold was significantly reduced after maximal secretory stimulation, but was found enhanced by 200 to 300 percent after supramaximal stimulation. No fine structural alterations at junctional complexes or at both the lateral and luminal plasma membranes were observed after maximal stimulation except an increased number of exocytotic figures at the luminal face. However, supramaximal stimulation led to progressive rarefaction of the tight junctional network and disintegration of the gap junctions. Concomitantly, an equal distribution of membrane particles on both faces of the plasma membrane together with a random occurrence of exocytotic figures were observed.

Amino Acids↗
PubMed2002

Peptide design using omega-amino acids: unusual turn structures nucleated by an N-terminal single gamma-aminobutyric acid residue in short model peptides.

Incorporation of omega-amino acids into peptide sequences plays an important role in designing peptides with modified backbone conformation and enhanced stability against proteolysis. The present study establishes the presence of unusual turns involving 12-membered hydrogen bonded rings in terminally blocked tri- and tetrapeptides. X-ray diffraction analysis of single crystals and NMR studies have been used to probe the three-dimensional structures of two terminally protected short peptides, Boc-gamma-Abu(1)-Aib(2)-Ala(3)-OMe 1 and Boc-gamma-Abu(1)-Aib(2)-Ala(3)-Aib(4)-OMe 2 (gamma-Abu = gamma-aminobutyric acid), in which conformationally flexible omega-amino acids (gamma-Abu) and conformationally restricted alpha-aminoisobutyric acid (Aib) residues are positioned contiguously. The crystal structures of both peptides 1 and 2 exhibit unusual turns composed of 12-membered hydrogen bonded rings involving C [double bond] O from the Boc-group and Ala(3) NH. A type I' beta-turn was observed in the structure of peptide 2 adjacent to the unusual turn with a hydrogen bond between gamma-Abu(1) C [double bond] O and Aib(4) NH. The crystals of peptide 1 are in the space group P2(1), a = 9.3020(10) A, b = 23.785(2) A, c = 10.022(3) A, beta = 101.35 degrees(4), Z = 4, R = 5.7%, and R(w) = 14.5%. Similarly, the crystals of peptide 2 are in the space group C2, a = 19.0772(6) A, b = 8.7883(2) A, c = 16.7758(3) A, beta = 110.7910 degrees(10), Z = 4, R = 6.71%, and R(w) = 15.11%. The unusual turn in both peptides 1 and 2 are retained in solution as is evident from NMR studies in CDCl(3). The role of the adjacently located Aib residue to nucleate the 12-membered hydrogen bonded ring is also addressed.

Amino Acids↗
PubMed2001

Extraterrestrial amino acids in Orgueil and Ivuna: tracing the parent body of CI type carbonaceous chondrites.

Amino acid analyses using HPLC of pristine interior pieces of the CI carbonaceous chondrites Orgueil and Ivuna have found that beta-alanine, glycine, and gamma-amino-n-butyric acid (ABA) are the most abundant amino acids in these two meteorites, with concentrations ranging from approximately 600 to 2,000 parts per billion (ppb). Other alpha-amino acids such as alanine, alpha-ABA, alpha-aminoisobutyric acid (AIB), and isovaline are present only in trace amounts (<200 ppb). Carbon isotopic measurements of beta-alanine and glycine and the presence of racemic (D/L approximately 1) alanine and beta-ABA in Orgueil suggest that these amino acids are extraterrestrial in origin. In comparison to the CM carbonaceous chondrites Murchison and Murray, the amino acid composition of the CIs is strikingly distinct, suggesting that these meteorites came from a different type of parent body, possibly an extinct comet, than did the CM carbonaceous chondrites.

Journal Article↗
PubMed1994

Lysine transport in lactating rat mammary tissue: evidence for an interaction between cationic and neutral amino acids.

The transport of lysine by the lactating rat mammary gland has been examined to determine whether there is an interaction between cationic and neutral amino acids. Lysine uptake was time dependent and unaffected by replacing Na+ with choline. In the presence of Na+, lysine influx was inhibited by cationic amino acids (arginine, homoarginine, ornithine and lysine) and by a range of neutral amino acids (methionine, glutamine, leucine, phenylalanine, alanine, asparagine, alpha-aminoisobutyric acid (AIB), 2-aminobicyclo [2,2,1] heptane-2-carboxylic acid (BCH), proline and tryptophan). Leucine and glutamine also inhibited lysine influx in the absence of Na+ but phenylalanine and proline did not. Lysine efflux from mammary tissue was trans-accelerated by various cationic amino acids (lysine, arginine, homoarginine and ornithine). In addition, leucine and glutamine were capable of trans-stimulating lysine efflux in the presence and absence of Na+. It appears that cationic and neutral amino acids stimulated lysine efflux at a single locus.

Amino Acids↗
PubMed2000

Amino acid transport into cultured McCoy cells infected with Chlamydia trachomatis.

Amino acid transport into McCoy cells infected with strains representative of the two major biovars of Chlamydia trachomatis has been studied to determine if uptake is increased during infection. Preliminary work suggested that the transport systems L, A/ASC (for neutral amino acid transport), N (for transport of Asn, Gln, and His) and y+ (for cationic amino acids) were present in McCoy cells. With lymphogranuloma venereum biovar strain 434, little difference in the influx of representative amino acids Trp, His, and Lys or the analogue 2-aminoisobutyric acid (AIB) was observed during infection. With trachoma biovar strain DK20, a small increase in the initial entry rate and equilibrium concentration of each amino acid was found. McCoy cells appear to have great capacity for concentrating amino acids, which might obviate the need for transport induction by chlamydiae under conditions favoring the growth of infectious organisms.

Amino Acids↗
PubMed2002

Short-term effects of thyroid hormones and 3,5-diiodothyronine on membrane transport systems in chick embryo hepatocytes.

Rapid nongenomic effects of thyroid hormones L-T(3) and L-T(4) on two plasma membrane transport systems were investigated in 14-d-old and 19-d-old chick embryo hepatocytes. The Na(+)/H(+) exchanger activity was measured using the intracellular pH-sensitive fluorescent probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester, whereas the amino acid transport was estimated by [1-(14)C]-2-aminoisobutyric acid uptake. System A amino acid transport activation was linear to hormone concentration, whereas the Na/H exchanger gave a bell-shaped dose-response curve, with a maximum at the physiological hormone concentration of 1 nM. The specificity of the effect was verified by the use of inhibitors and analogues. The thyroid hormone analog 3,5-diiodo-L-thyronine was able to mimic some of the hormone effects, but with a lower efficiency. The effect on the Na(+)/H(+) exchanger was identified for 14-d-old and 19-d-old cells, whereas the amino acid transport could only be activated at the late stage of embryo development. Both transport systems were activated through a signal transduction pathway involving PKC, MAPK pathway, and PI3K, even though the differences in response behavior indicate a differential modulation of the two transport systems by L-T(3) and L-T(4). These results clearly demonstrate the existence of rapid nongenomic action of thyroid hormones also in avian cells, and show that activation of System A amino acid transport is not directly correlated to changes in intracellular pH. For the first time, evidence is presented which suggests that short-term effects of thyroid hormones may play a role during fetal development and cell differentiation.

Amino Acids↗
PubMed1999

Identification of unusual amino acids in peptides using automated sequential Edman degradation coupled to direct detection by electrospray-ionization mass spectrometry.

The determination of the primary structure of peptides and proteins is routine in many laboratories; however, many of the obtained sequences are incomplete or can be misinterpreted when the samples contain unusual amino acids. Here we report the development of an automated peptide sequenator coupled to an electrospray-ionization (ESI) mass spectrometer (MS) that, in conjunction with minor modifications to the sequencing conditions and, in some cases, prior derivatization of amino acids, allows the detection of the phenylthiohydantoin (PTH) derivatives of a number of unusual amino acids. Using the coupled sequenator-ESI-MS system we were able to determine the complete sequence of the lantibiotic gallidermin, a partial sequence of the calcium-dependent peptide antibiotic CDA2 as well as the pool sequence of a mixture of synthetic peptides containing nonproteinogenic amino acids. In addition to the 20 proteinogenic amino acids, the procedure was able to detect PTH derivatives of hydroxyphenylglycine, 2,3-didehydroasparagine, 3-methylglutamic acid, oxytryptophan, ornithine, N-methylglycine, dihydroxyphenylalanine, and alpha-aminoisobutyric acid. Similarly, after a simple derivatization procedure, we were also able to correctly identify educts of 2,3-didehydroalanine, 2,3-didehydrobutyrine, lanthionine, and 3-methyllanthionine.

Amino Acid Sequence↗
PubMed1999

The effect of burn subeschar tissue fluid on skeletal muscle and hepatic amino acid uptake in an experimental system in vitro.

Burn injury is associated with major metabolic disturbances. Many factors or mediators are responsible for post-burn metabolic changes. The present study was designed to test the role of interstitial edema fluid from burn eschar in regulating amino acid transport into hepatic and muscle tissue. Subeschar tissue fluid (SEF) was collected from just under the full thickness burn area. Amino acid transport, determined as the uptake of [3H]-alpha-aminoisobutyric acid by incubated soleus muscles or liver slices in vitro, was reduced after the addition of subeschar tissue fluid. The suppression was more marked with fluids taken from patients with a large burn area. Significant findings were noted when the total surface burn area was more than 70%. There were significant differences in the SEF suppression effect between survivors and non-survivors, but not between inhalation and non-inhalation victims. The results suggest the presence of one or more factors in subeschar tissue fluid that inhibit both muscle and liver amino acid transport. The data also suggest that the inhibitory factors are most likely produced by the burned tissue. This suppression effect may be beneficial to burn victims in maintaining near-normal vascular osmolarity by way of an increased plasma amino acid level.

Adult↗
PubMed1979

Active amino acid absorption by proximal convoluted and proximal straight tubules.

Transport of glycine and alpha-aminoisobutyric acid (AIB) was studied in proximal convoluted (PCT) and proximal straight (PST) tubules isolated from rabbit kidney. In both segments, unidirectional lumen-to-bath fluxes (J1 leads to b) (pmol min-1mm-1) of glycine and AIB exceeded corresponding bath-to-lumen fluxes (Jb leads to 1), which demonstrated that both were actively absorbed. During J1 leads to b measurements, intracellular concentrations of both amino acids were greater than the luminal concentration, indicating that the site of active transport was the luminal membrane. Replacement of Na+ by choline in both perfusate and bath (PCT) or perfusate alone (PST) reduced J1 leads to b for glycine to equal Jb leads to 1. Nonlinear fitting of the relationship between J1 leads to b and the mean luminal glycine concentration according to Michaelis-Menten kinetics gave Jmax values of 28.5 (PCT) and 2.5 (PST) pmol min-1 mm-1, and Km values of 11.8 (PCT) and 0.7 (PST) mM. There was a parallel, Na+-independent, nonsaturable component of J1 leads to b characterized by an apparent permeability coefficient of 0.19 micron/s in the PCT and 0.04 micron/s in the PST.

Absorption↗
PubMed2003

Effect of alpha,alpha-dialkyl amino acids on the protease resistance of peptides.

A tryptic [EC 3.4.21.4] digestion assay of 2-aminoisobutyric acid (Aib)-containing peptides was carried out to investigate the effect of alpha,alpha-dialkyl amino acid residues on the protease resistance. The introduction of Aib residues to the P1' positions exhibited a 19-fold higher protease resistance than the peptide with Aib residues introduced to the P2 position or the non-Aib peptide. The peptide having Aib residues introduced to the P1' and P2 positions resulted in complete resistance.

Amino Acids, Branched-Chain↗
PubMed1975

Amino acid and sugar transport incells permissively infected with simian virus 40.

Transport of alpha-aminoisobutyric acid and 2-deoxy-D-glucose in African green monkey kidney cells was measured 8 to 100 hr following permissive simian virus 40 infection. No differences in transport were detected during the time-period studies, and no significant differences were seen between the apparent Michaelis-Menten constants of normal and virally infected cells. The absence of transport enhancement in permissive simian virus 40 infection suggests that the augmented transport of viral-transformed cell lines devolves upon altered host genome function.

Aminobutyrates↗
PubMed2005

Acute blood-brain barrier opening in experimentally induced focal cerebral ischemia is preferentially identified by quantitative magnetization transfer imaging.

Pathologic changes in brain tissue during and after stroke may lead to injury of the blood-brain barrier (BBB) and subsequent hemorrhagic transformation (HT). In a rat model of HT, the apparent diffusion coefficient of water, cerebral blood flow, relaxation times, T(1) and T(2), and magnetization transfer (MT) related parameters (T(1sat), K(for) and the MT ratio) were repetitively measured during 3 h of focal ischemia and 2 h of reperfusion (n = 8). Areas of BBB opening were identified by sequential assay of the transcapillary influx of Gd-diethylenetriaminepentaacetic acid (Gd-DTPA) by MRI and (14)C-alpha-aminoisobutyric acid (AIB) by quantitative autoradiography. Ischemia-injured regions of interest were identified from the MRI data and divided into those with and without BBB opening. Of the several MRI parameters measured, the T(1sat) in the caudate-putamen and preoptic area during ischemia and the first 2 h of reperfusion correlated best with the regional pattern of BBB opening observed thereafter. These data suggest that an ipsilateral/contralateral T(1sat) ratio > 1.6 demarcates leakage of small molecules such as Gd-DTPA and AIB across the BBB. As to clinical relevance, the quantitation of MT parameters in acute stroke may enable the early detection of areas of BBB opening and potential HT.

Acute Disease↗