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101.
S M Czerwinski T T Kurowski E E McKee R Zak R C Hickson 《Journal of applied physiology》1991,70(1):300-305
One aim of this investigation was to determine whether the cardiac enlargement observed with glucocorticoid treatment is temporary or remains a permanent adaptation if steroid treatment is prolonged. A second aim was to study whether myosin heavy chain (MHC) synthesis rates are coordinated with the cardiac mass responses. Female rats received either a vehicle (1% aqueous carboxymethyl cellulose in saline) or hydrocortisone 21-acetate for 1, 3, 7, 11, and 15 days. Peak cardiac enlargement (10-15%) was observed after 7 days of hormone treatment in two separate series of experiments. The enlargement was maintained through 11 days of steroid injections but by 15 days had declined toward control levels. MHC synthesis measurements were performed by constant infusion of [3H]leucine. Leucine specific activities were similar among precursor pools (intracellular, extracellular, and leucyl-tRNA) and did not vary with steroid treatments. Fractional synthesis rates of ventricular MHC (%/day) did not change during the period of increase in ventricular mass but were reduced to 56-59% of controls (-11/19.5) at 7 and 11 days of treatment, when ventricular mass increases were highest. MHC breakdown (%/day) was reduced to approximately 60% (-11.5/18.7) of controls at 7 and 11 days. Changes in total protein synthesis, which was measured in isolated perfused hearts, were similar to the MHC responses and indicated that the alterations in MHC synthesis are synchronized with the hormonal effects on total protein metabolism. These results demonstrate that peak cardiac enlargement is not maintained with long-term glucocorticoid treatment.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
102.
Summary The use of conjugates of microbial iron chelators (siderophores) and antibiotics for illicit transport of antibiotics into cells is a potentially powerful method for the rational design of therapeutic agents. The structural complexity of most natural siderophores has impeded progress in this area. Described here are the design, syntheses and preliminary biological studies of several siderophore--lactam antibiotic conjugates. Both hydroxamic-acid-based and catechol-based conjugates with and without amino acid spacers to carbacephalosporins were synthesized and demonstrated to be effective inhibitors ofEscherichia coli X580. Mutant selection was noted for each class of conjugates. Mutants selected from exposure of theE. coli to the hydroxamate conjugates were susceptible to the catechol conjugates and vice versa. Combinations of hydroxamate-and catechol-carbacephalosporin conjugates were most effective inhibitors ofE. coli X580. 相似文献
103.
Benjamin Salmon Claire Bardet Mayssam Khaddam Jiar Naji Benjamin R. Coyac Brigitte Baroukh Franck Letourneur Julie Lesieur Franck Decup Dominique Le Denmat Antonino Nicoletti Anne Poliard Peter S. Rowe Eric Huet Sibylle Opsahl Vital Agnès Linglart Marc D. McKee Catherine Chaussain 《PloS one》2013,8(2)
Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide − a substrate for PHEX and a strong inhibitor of mineralization − derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic target. 相似文献
104.
105.
Víctor Faundes William G. Newman Laura Bernardini Natalie Canham Jill Clayton-Smith Bruno Dallapiccola Sally J. Davies Michelle K. Demos Amy Goldman Harinder Gill Rachel Horton Bronwyn Kerr Dhavendra Kumar Anna Lehman Shane McKee Jenny Morton Michael J. Parker Julia Rankin Siddharth Banka 《American journal of human genetics》2018,102(1):175-187
106.
Endocrine regulation of energy metabolism by the skeleton 总被引:23,自引:0,他引:23
Lee NK Sowa H Hinoi E Ferron M Ahn JD Confavreux C Dacquin R Mee PJ McKee MD Jung DY Zhang Z Kim JK Mauvais-Jarvis F Ducy P Karsenty G 《Cell》2007,130(3):456-469
The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism. 相似文献
107.
Jorgensen TN McKee A Wang M Kushnir E White J Refaeli Y Kappler JW Marrack P 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(6):3417-3424
The life and death of T cells is controlled to a large extent by the relative amounts of Bcl-2-related proteins they contain. The antiapoptotic protein Bcl-2 and the proapoptotic protein Bim are particularly important in this process with the amount of Bcl-2 per cell dropping by about one-half when T cells prepare to die. In this study we show that Bcl-2 and Bim each control the expression of the other. Absence of Bim leads to a drop in the amount of intracellular Bcl-2 protein, while having no effect on the amounts of mRNA for Bcl-2. Conversely, high amounts of Bcl-2 per cell allow high amounts of Bim, although in this case the effect involves increases in Bim mRNA. These mutual effects occur even if Bcl-2 is induced acutely. Thus these two proteins control the expression of the other, at either the protein or mRNA level. 相似文献
108.
Cantin LD Magnuson S Gunn D Barucci N Breuhaus M Bullock WH Burke J Claus TH Daly M Decarr L Gore-Willse A Hoover-Litty H Kumarasinghe ES Li Y Liang SX Livingston JN Lowinger T Macdougall M Ogutu HO Olague A Ott-Morgan R Schoenleber RW Tersteegen A Wickens P Zhang Z Zhu J Zhu L Sweet LJ 《Bioorganic & medicinal chemistry letters》2007,17(10):2869-2873
Modulation of cAMP levels has been linked to insulin secretion in preclinical animal models and in humans. The high expression of PDE-10A in pancreatic islets suggested that inhibition of this enzyme may provide the necessary modulation to elicit increased insulin secretion. Using an HTS approach, we have identified quinoline-based PDE-10A inhibitors as insulin secretagogues in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured. 相似文献
109.
West Coast prairies in the US are an endangered ecosystem, and effective conservation will require an understanding of how
changing climate will impact nutrient cycling and availability. We examined how seasonal patterns and micro-heterogeneity
in edaphic conditions (% moisture, total organic carbon, % clay, pH, and inorganic nitrogen and phosphorus) control carbon,
nitrogen, and phosphorus cycling in an upland prairie in western Oregon, USA. Across the prairie, we collected soils seasonally
and measured microbial respiration, net nitrogen mineralization, net nitrification, and phosphorus availability under field
conditions and under experimentally varied temperature and moisture treatments. The response variables differed in the degree
of temperature and moisture limitation within seasons and how these factors varied across sampling sites. In general, we found
that microbial respiration was limited by low soil moisture year-round and by low temperatures in the winter. Net nitrogen
mineralization and net nitrification were never limited by temperature, but both were limited by excessive soil moisture in
winter, and net nitrification was also inhibited by low soil moisture in the summer. Factors that enhanced microbial respiration
tended to decrease soil phosphorus availability. Edaphic factors explained 76% of the seasonal and spatial variation in microbial
respiration, 35% of the variation in phosphorus availability, and 29% of the variation in net nitrification. Much of the variation
in net nitrogen mineralization remained unexplained (R
2 = 0.19). This study, for the first time, demonstrates the complex seasonal controls over nutrient cycling in a Pacific Northwest
prairie. 相似文献
110.