Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The Brown Norway (B/N) Katholiek rat is a mutant strain of plasma kininogen deficiency. The plasma of B/N-Katholiek rats was shown to contain only 3-5% of high-molecular-weight and low-molecular-weight kininogens (HK and LK) of the normal level by specific RIA, and 30% of prekallikrein was detected by amidase activity. However, HK antigen in the liver microsomal fraction of B/N-Katholiek rats was about 60% of that of normal rats. 2. In this paper we compare and discuss synthesis and secretion of HK and LK by primary cultures of livers of deficient and normal rats. The deficient hepatocytes could synthesize HK and LK in the same way as normal cells but could not secrete mature forms of HK and LK in the medium. Examination of the subcellular localization of the mutant HK in the hepatocytes showed that a larger amount of mutant HK antigen, compared to normal rats, was found in the 10,000 g fraction, which is rich in lysosomes, suggesting that the mutant HK may be transported to the lysosomes. 3. We also analyzed sequence of the HK cDNA of B/N-Katholiek and B/N-Kitasato rats and found a point mutation of G to A at nucleotide 487, which locates at the heavy chain region of HK and LK. 4. We constructed five expression plasmids to transfect COS-1 cells to examine HK secretion. COS-1 cells transfected with the plasmids containing the G to A transition could not secrete and retained HK, while those cells transfected with the plasmids containing normal G released HK into the medium. 5. These results indicate that a point mutation G to A at nucleotide 487, resulting in an amino acid transition from alanine (163) to threonine, is responsible for the defective secretion of HK and LK by the liver of B/N-Katholiek rats. We also discuss other cases of secretion defect of plasma proteins reported in the literature.
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PMID:Molecular mechanism of kininogen deficiency in brown Norway Katholiek rats. 774 70

Brown Norway Katholiek (B/N-Ka) is a mutant rat strain deficient in plasma high-molecular-weight (HK) and low-molecular-weight kininogen (LK). It has been reported that the deficiency, caused by defective secretion of HK and LK by the liver, is associated with a point mutation of alanine (163) to threonine in the common heavy chain. In this report we demonstrate by specific radioimmunoassay that the amount of immunoreactive HK antigen in the B/N-Ka kidney was almost the same as that found in the normal Brown Norway rat (Brown Norway Kitasato, B/N-Ki). HK antigen in the kidneys of both strains was immunohistochemically localized at distal tubules with similar intensity in both strains. Among the subcellular fractions of the kidney homogenates, HK antigen was predominantly found in the microsomal fraction of both strains. To see whether this HK antigen is derived from plasma HK or is synthesized in the kidneys, we examined uptake of HK by the tubular cells after incubation with 125I-HK. Only 0.6% of the radioactivity of added 125I-HK was found in the tubular cells of both strains after a 60-min incubation. Messages of HK mRNA from both strains of rats were visualized by PCR at almost the same intensity. These results suggest that HK antigen found in the kidney may be derived mainly from biosynthesis in the kidney itself and partly from uptake of HK from blood. There was no difference in these features of HK between the kidneys of the deficient and the normal B/N rats.
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PMID:Demonstration of high-molecular-weight kininogen in kininogen-deficient rat kidneys. 779 87

To clarify the mechanism of the secretion defect of high molecular weight kininogen (HK) and low molecular weight kininogen (LK) by the liver of Brown Norway (B/N) Katholiek rats causing plasma kininogen deficiency, we cloned cDNAs for HK from cDNA libraries of the livers of B/N Katholiek and B/N Kitasato rats. A point mutation of G to A at nucleotide 487 was found in the cDNA of B/N Katholiek rats by sequence analysis of the cDNAs (including the entire HK-coding region) obtained from both strains. Both B/N Katholiek and B/N Kitasato rat cDNA fragments were introduced into a eukaryotic vector, pRc/CMV, to construct their respective expression plasmid, which was used to transfect COS-1 cells. At 24 h of incubation, the culture medium of COS-1 cells transfected with the B/N Katholiek rat cDNA contained only 10% of the HK antigen that was found in COS-1 cells transfected with the B/N Kitasato rat cDNA. More HK antigen was retained in the former cells. Moreover, cells transfected with B/N Katholiek rat cDNA, in which the A at nucleotide 487 was artificially replaced by G, secreted a significant amount of HK into the medium. These results suggest that a point mutation of G to A at nucleotide 487, which causes a substitution of Ala163 to Thr in the heavy chain of HK and LK, is responsible for the defective secretion of HK and LK by the liver of B/N Katholiek rats.
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PMID:A point mutation of alanine 163 to threonine is responsible for the defective secretion of high molecular weight kininogen by the liver of brown Norway Katholiek rats. 834 7

When the protonated retinal Schiff base dissociates in the photocycle of the proton pump bacteriorhodopsin, asp-85 is the proton acceptor. Replacing this residue with threonine confers halorhodopsin-like properties on the protein, including chloride transport [Sasaki, J., Brown, L.S., Chon, Y.-S., Kandori, H., Maeda, A., Needleman, R., & Lanyi, J.K. (1995) Science 269, 73-75]. However, the electrostatic interaction between the vicinity of residue 85 and glu-204, a residue located about 10 A away near the extracellular surface, that is a part of the proton transport mechanism, should still exist. We find that in the D85T mutant glu-204 becomes protonated when chloride is added. This indicates that the binding of chloride at thr-85 must be equivalent to deprotonation of asp-85. The protonation state of glu-204 reports therefore on the presence or absence of chloride bound at thr-85. During the chloride-transport cycle of D85T, but not D85T/E204Q, fluorescein and pyranine detect the transient release of protons from the protein to the surface and the bulk. The release and the subsequent uptake of the protons occur during the rise and decay of a red-shifted photointermediate, respectively, and confirm the earlier suggestion that this state has the same role in the chloride transport as the M intermediate in the proton transport. Consistent with the red-shift of the absorption maximum, the chloride bound near the Schiff base had already moved away, presumably to be released at the cytoplasmic surface, but another chloride ion has not yet been taken up from the extracellular surface. The switch of the connectivity of the chloride binding site from the cytoplasmic to the extracellular membrane surface must occur therefore during the lifetime of this photointermediate.
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PMID:Interaction of proton and chloride transfer pathways in recombinant bacteriorhodopsin with chloride transport activity: implications for the chloride translocation mechanism. 897 74

Recently we reported a novel means of regulating LIM domain protein function. Paxillin LIM zinc-finger phosphorylation in response to cell adhesion regulates the subcellular localization of this cytoskeletal adaptor protein to focal adhesions, and also modulates cell adhesion to fibronectin (Brown et al. [1998] Mol. Biol. Cell 9:1803-1816). In the present study, we characterize further the protein kinases that phosphorylate paxillin LIM2 on threonine and LIM3 on serine. Analysis of the subcellular distribution of the LIM kinases demonstrated that the LIM3 protein kinase, but not the LIM2 kinase, resides within a detergent-insoluble fraction. The activities of the paxillin LIM domain kinases are differentially regulated during embryogenesis, and analysis of tissue distribution indicated a specificity in expression patterns between the LIM2 and LIM3 kinases. In addition, these protein kinases were refractory to inhibition by a panel of broad-spectrum serine/threonine kinase inhibitors, suggesting a novel derivation. The paxillin protein kinase activities were stimulated in serum-starved CHO.K1 cells by the mitogen phorbol myristate acetate (PMA), and by PMA and angiotensin II in rat aortic smooth muscle cells. In vivo labeling, phosphoamino acid analysis, and phosphopeptide mapping of paxillin immunoprecipitated from angiotensin II-stimulated smooth muscle cells confirmed an induction of paxillin serine/threonine phosphorylation and supports the contention that these newly identified paxillin kinases are dynamic components of growth factor signaling through the cytoskeleton.
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PMID:Characterization of paxillin LIM domain-associated serine threonine kinases: activation by angiotensin II in vascular smooth muscle cells. 1058 Oct 4

1. The aim of this study was to determine the nitrogen balance and the performance of laying hens fed on diets with a protein content lower than the diets currently used in commercial practice but with adequate concentrations of lysine, sulphur amino acids, tryptophan and threonine. 2. Ninety-six Hy-Line Brown hens, 24 weeks old, were divided into 3 groups of 8 replicates and received, for 16 weeks, diets formulated to have 3 different protein concentrations: 170 (control), 150 and 130 g/kg CP and the same energy content. For each protein concentration, the contents of lysine, methionine, methionine+cystine, tryptophan and threonine were maintained at minimum requirement concentrations by supplying synthetic amino acids. 3. In the first half of the trial, egg production and egg weight were similar in all groups. From the 9th week onwards group 150 CP laid heavier eggs and had a slightly lower egg deposition and total mass. Food conversion ratio was best in the control group. 4. Nitrogen intake was related to the protein concentration of the diet, the food intake being almost the same in the 3 experimental groups. Faecal nitrogen content significantly and linearly decreased with reduction in dietary protein content and was about 50% of the intake. Considering the nitrogen faecal/intake ratio, the 150 CP group showed better nitrogen utilisation at each sampling time.
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PMID:Nitrogen retention and performance of brown laying hens on diets with different protein content and constant concentration of amino acids and energy. 1142 31

Skeletal muscle insulin sensitivity improves with short-term reduction in calorie intake. The goal of this study was to evaluate changes in the abundance and phosphorylation of Akt1 and Akt2 as potential mechanisms for enhanced insulin action after 20 days of moderate calorie restriction [CR; 60% of ad libitum (AL) intake] in rat skeletal muscle. We also assessed changes in the abundance of SH2 domain-containing inositol phosphatase (SHIP2), a negative regulator of insulin signaling. Fisher 344 x Brown Norway rats were assigned to an AL control group or a CR treatment group for 20 days. Epitrochlearis muscles were dissected and incubated with or without insulin (500 microU/ml). Total Akt serine and threonine phosphorylation was significantly increased by 32 (P < 0.01) and 30% (P < 0.005) in insulin-stimulated muscles from CR vs. AL. Despite an increase in total Akt phosphorylation, there was no difference in Akt1 serine or Akt1 threonine phosphorylation between CR and AL insulin-treated muscles. However, there was a 30% decrease (P < 0.05) in Akt1 abundance for CR vs. AL. In contrast, there was no change in Akt2 protein abundance, and there was a 94% increase (P < 0.05) in Akt2 serine phosphorylation and an increase of 75% (P < 0.05) in Akt2 threonine phosphorylation of insulin-stimulated CR muscles compared with AL. There was no diet effect on SHIP2 abundance in skeletal muscle. These results suggest that, with brief CR, enhanced Akt2 phosphorylation may play a role in increasing insulin sensitivity in rat skeletal muscles.
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PMID:Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated rat skeletal muscle. 1279 17

Physical forces are important regulators of vascular structure and function though it is unknown how aging may affect the ability of the vasculature to respond to mechanical stimuli. We investigated the pressure-induced activation of ribosomal S6-kinase (p70S6k) and its pathway-related proteins (Akt, GSK-3beta, SHP-2, PTEN) in aortae from young adult (6 month), aged (30 month), and very aged (36 month) Fischer 344 x Brown Norway F1 hybrid rats. With aging, the aortic tissue content of Akt. SHP-2, and PTEN was significantly increased while total p70S6k and GSK-3beta were unchanged. By comparison, the basal phosphorylation of p70S6k at Thr 389 and Thr 421/Ser 424 was increased ( approximately 40%) and unchanged, respectively, while Akt decreased (approximately 37%), GSK-3beta was unchanged, SHP-2 increased (approximately 73.5%), and PTEN increased (approximately 120%) in the aortae of very aged rats. Acute pressurization of aortae resulted in similar increases in phosphorylation of Akt among the different age groups. By comparison, pressure-induced phosphorylation of p70S6k at Thr 389, GSK-3beta and SHP-2 decreased; whereas, PTEN dephosphorylation was increased in 36-month versus 6-month aortae. The results indicate marked alterations in the p70S6k signaling pathway with aging. The implications of these findings on age-associated vessel remodeling are discussed.
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PMID:Aging alters vascular mechanotransduction: pressure-induced regulation of p70S6k in the rat aorta. 1608 21

GalNAc-transferase can catalyze the biosynthesis of O-linked oligosaccharides. The specificity of GalNAc-transferase is composed of nine amino acid residues denoted by R4, R3, R2, R1, R0, R1', R2', R3', R4'. To predict whether the reducing monosaccharide will be covalently linked to the central residue R0(Ser or Thr), a new method based on feature selection has been proposed in our work. 277 nonapeptides from reference [Chou KC. A sequence-coupled vector-projection model for predicting the specificity of GalNAc-transferase. Protein Sci 1995;4:1365-83] are chosen for training set. Each nonapeptide is represented by hundreds of amino acid properties collected by Amino Acid Index database (http://www.genome.jp/aaindex) and transformed into a numeric vector with 4554 features. The Maximum Relevance Minimum Redundancy (mRMR) method combining with Incremental Feature Selection (IFS) and Feature Forward Selection (FFS) are then applied for feature selection. Nearest Neighbor Algorithm (NNA) is used to build prediction models. The optimal model contains 54 features and its correct rate tested by Jackknife cross-validation test reaches 91.34%. Final feature analysis indicates that amino acid residues at position R3' play the most important role in the recognition of GalNAc-transferase specificity, which were confirmed by the experiments [Elhammer AP, Poorman RA, Brown E, Maggiora LL, Hoogerheide JG, Kezdy FJ. The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase as inferred from a database of in vivo substrates and from the in vitro glycosylation of proteins and peptides. J Biol Chem 1993;268:10029-38; O'Connell BC, Hagen FK, Tabak LA. The influence of flanking sequence on the O-glycosylation of threonine in vitro. J Biol Chem 1992;267:25010-8; Yoshida A, Suzuki M, Ikenaga H, Takeuchi M. Discovery of the shortest sequence motif for high level mucin-type O-glycosylation. J Biol Chem 1997;272:16884-8]. Our method can be used as a tool for predicting O-glycosylation sites and for investigating the GalNAc-transferase specificity, which is useful for designing competitive inhibitors of GalNAc-transferase. The predicting software is available upon the request.
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PMID:GalNAc-transferase specificity prediction based on feature selection method. 1895 94

Reliable parameters assessing graft function are essential for the prediction of graft outcome after liver transplantation. Many studies have focused on genomics, transcriptomics, and proteomics using classical methods such as polymerase chain reaction (PCR), Western blotting, etc. Metabonomics is a new area and perspective in the transplantation arena. Little research results regarding metabolism have been achieved; however, serum metabolite profiles from early acute liver rejection models are less well understood. A model of nonarteralized orthotopic liver transplantation (OLT) using Lewis to Brown Norway (BN) rats was preformed. We investigated the variation of serum metabolites by gas chromatography-mass spectrometry (GC-MS) and correlated this change to morphological changes of liver allografts at time points including days 1, 3, 7, and 10 posttransplantation. A significant decrease in serum glucose as well as increase in serum hexadecanoic acid, octadecanoic acid, cholesterol, proline, and threonine have been observed in the serum following transplantation. The total trend in PCA illustrated that serum metabonomic profiles are correlated with the pathological changes seen following liver transplantation. The results of this study suggest that changes in metabonomic profiles reflected in the graft injury are correlated with histological changes instead of classical liver function using traditional biochemical examination. PCA provides support to the investigation of early acute rejection and could become a useful clinical standard in diagnosing the end states of patient. Metabonomics is an efficient technique for detecting graft injury in the early phases of acute rejection.
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PMID:Metabonomic profile of rats with acute liver rejection. 1919 2


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