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991.
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Morissette G Sabourin T Adam A Marceau F 《Canadian journal of physiology and pharmacology》2006,84(11):1107-1119
Bradykinin (BK)-related peptides are suspected to negatively influence diverse functions in vascular smooth muscle cells (SMCs), notably via stimulation of the inducible B1 receptor (B1R), and have been shown to inhibit the migration of rat SMCs. The present study had several objectives: (i) to test whether B1R mediates the inhibition of migration of arterial SMCs from additional species (the human and the rabbit); (ii) whether B1R density influences this action and whether autocrine NO or prostanoid release modulate it; and (iii) the possible signaling interaction between the B1R and phosphatidylinositol-3 kinase (PI-3K) has been addressed. The peptidase resistant B1R agonist Sar-[D-Phe8]des-Arg9-BK (10 nmol/L - 1 micromol/L) was an inhibitor of migration in human or rabbit arterial SMCs in a wound closure assay, more effectively if the medium composition allowed a high B1R expression (20% fetal bovine serum (FBS) + interleukin-1beta (IL-1beta) in human SMCs, 10% FBS in rabbit cells). The effect of the B1R agonist on motility was abrogated by a B1R antagonist, B-9858, but not by the B2R antagonist Hoe 140; a peptidase-resistant B2R agonist, [Phe8Psi(CH2-NH)-Arg9]BK, had a marginal or no effect on migration. Sar-[D-Phe8]des-Arg9-BK (1 micromol/L) did not significantly influence SMC proliferation. The B1R-mediated inhibition of SMC migration was not affected by pharmacological inhibition of the nitric oxide synthases or cyclooxygenases-1 or -2, but was correlated to an inhibition of PI-3K in both types of SMCs. The inhibition of SMC migration mediated by the kinin B1R is likely independent from NO or prostanoid release, applicable to several species, and correlated to receptor density and the inhibition of PI-3K. 相似文献
994.
Grijalvo S Bedia C Triola G Casas J Llebaria A Teixidó J Rabal O Levade T Delgado A Fabriàs G 《Chemistry and physics of lipids》2006,144(1):69-84
The synthesis of novel N-acylethanolamines and their use as inhibitors of the aCDase is reported here. The compounds are either 2-oxooctanamides or oleamides of sphingosine analogs featuring a 3-hydroxy-4,5-hexadecenyl tail replaced by ether or thioether moieties. It appears that, within the 2-oxooctanamide family, the C3-OH group of the sphingosine molecule is required for inhibition both in vitro and in cultured cells. Furthermore, although the (E)-4 double bond is not essential for inhibitory activity, the (E) configuration is required, since the analogue with a (Z)-4 unsaturation was not inhibitory. None of the oleamides inhibited the aCDase in vitro. Conversely, with the exception of N-oleoylethanolamine and its analogs with S-decyl and S-hexadecyl substituents, all the synthesized oleamides inhibited the aCDase in cultured cells, although with a relatively low potency. We conclude that novel aCDase inhibitors can evolve from N-acylation of sphingoid bases with electron deficient-acyl groups. In contrast, chemical modification of the N-oleoylsphingosine backbone does not seem to offer an appropriate strategy to obtain aCDase inhibitors. 相似文献
995.
The European common lizard (Lacerta vivipara) tolerates long periods at sub-zero temperatures, either in the supercooled or the frozen state. Both physiological conditions limit oxygen availability to tissues, compelling lizards to cope with potential oxidative stress during the transition from ischemic/anoxic conditions to reperfusion with aerated blood during recovery. To determine whether antioxidant defenses are implicated in the survival of lizards when facing sub-zero temperatures, we monitored the activities of antioxidant enzymes and oxidative stress either during supercooling or during freezing exposures (20 h at -2.5 degrees C) and 24 h after thawing in two organs of lizards--muscle and liver. Supercooling induced a significant increase in the total SOD and GPx activity in muscle (by 67 and 157%, respectively), but freezing had almost no effect on enzyme activity, either in muscle or in liver. By contrast, thawed lizards exhibited higher GPx activity in both organs (a 133% increase in muscle and 59% increase in liver) and a significant decrease in liver catalase activity (a 47% difference between control and thawed lizards). These data show that supercooling (but not freezing) triggers activation of the antioxidant system and this may be in anticipation of the overgeneration of oxyradicals when the temperature increases (while thawing or at the end of supercooling). Oxidative stress was assessed from the content of 8-oxodGuo and the different DNA adducts resulting from lipid peroxidation, but it was unaltered whatever the physiological state of the lizards, thus demonstrating the efficiency of the antioxidant system that has been developed by this species. Overall, antioxidant defenses appear to be part of the adaptive machinery for reptilian tolerance to sub-zero temperatures. 相似文献
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997.
998.
Antimicrobial peptides from diverse families isolated from the skin of the Asian frog, Rana grahami 总被引:1,自引:0,他引:1
Conlon JM Al-Ghaferi N Abraham B Jiansheng H Cosette P Leprince J Jouenne T Vaudry H 《Peptides》2006,27(9):2111-2117
Seven peptides with antimicrobial activity were isolated in pure form from an extract of the skin of the Yunnanfu Kunming frog Rana grahami Boulenger, 1917. The peptides were identified as belonging to the nigrocin-2 (three peptides), brevinin-1 (one peptide), brevinin-2 (three peptides), and esculentin-1 (one peptide) families. Nigrocin-2GRb (GLFGKILGVGKKVLCGLSGMC) containing three lysine residues, represented the peptide with highest potency against microorganisms (MIC = 3 microM against Escherichia coli, 12.5 microM against Staphylococcus aureus and 50 microM against Candida albicans) and the greatest hemolytic activity against human erythrocytes (LD50 = 40 microM). In contrast, nigrocin-2GRa (GLLSGILGAGKHIVCGLSGLC) and nigrocin-2GRc (GLLSGILGAGKNIVCGLSGLC), with only a single lysine residue, showed weak antimicrobial and hemolytic activity. Phylogenetic relationships among Eurasian ranid frogs are less well understood than those of North American ranids but the primary structures of the R. grahami antimicrobial peptides suggest a close relationship of this species with the Japanese pond frogs R. nigromaculata and R. porosa brevipoda. 相似文献
999.
GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function
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Membrez M Hummler E Beermann F Haefliger JA Savioz R Pedrazzini T Thorens B 《Molecular and cellular biology》2006,26(11):4268-4276
GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations. 相似文献
1000.
Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer
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Annicotte JS Iankova I Miard S Fritz V Sarruf D Abella A Berthe ML Noël D Pillon A Iborra F Dubus P Maudelonde T Culine S Fajas L 《Molecular and cellular biology》2006,26(20):7561-7574
Peroxisome proliferator-activated receptor gamma (PPARgamma) might not be permissive to ligand activation in prostate cancer cells. Association of PPARgamma with repressing factors or posttranslational modifications in PPARgamma protein could explain the lack of effect of PPARgamma ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy. We show that the combination treatment impairs the bone-invasive potential of prostate cancer cells in mice. In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone. We show that E-cadherin expression responds only to the combination treatment and not to single PPARgamma agonists, defining a new class of PPARgamma target genes. These results open up new therapeutic perspectives in the treatment of prostate cancer. 相似文献