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131.
Suzuki Y Urano T Ihara H Nakajima T Nagai N Takada Y Taminato T Takada A 《Life sciences》2001,68(16):1827-1837
The effects of bezafibrate (PPAR alpha activator) and troglitazone (PPAR gamma activator) on the expression of plasminogen activator inhibitor type-1 (PAI-1) in HepG2 cells were investigated. Exposure of the cells for 24 hours to either oleic acid or insulin showed no obvious effects on PAI-1 synthesis, whereas the combination of the two agents induced a 2.3-fold increase in PAI-1 synthesis, which was accompanied by a 3-fold increase in both the 2.2 kb and 3.2 kb forms of PAI-1 mRNA. This up-regulation of PAI-1 synthesis was attenuated by bezafibrate in a dose-dependent manner (1-100 microM) with 30% reversal at 100 microM. In contrast, troglitazone further stimulated PAI-1 synthesis to 140% of the level obtained in the presence of both oleic acid and insulin. This attenuation by bezafibrate and enhancement by troglitazone required the presence of both oleic acid and insulin. It is interesting that PAI-1 expression was affected so differently by these two PPAR activators. 相似文献
132.
Ihara M Matsuda K Shimomura M Sattelle DB Komai K 《Bioscience, biotechnology, and biochemistry》2004,68(3):761-763
To compare the actions of clothianidin, a neonicotinoid acting on insect nicotinic acetylcholine receptors, and related compounds with that of imidacloprid, the compounds were tested on the Drosophila SAD-chicken beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. The maximum response of the SAD beta 2 nicotinic receptor to clothianidin was larger than that observed for acetylcholine. Ring breakage of the imidazolidine ring of imidacloprid resulting in the generation of a guanidine group was critical for this super agonist action. 相似文献
133.
Yusuke?Adachi Jiro?Yoshida Yukihiro?Kodera Akira?Kato Yutaka?Yoshikawa Yoshitane?Kojima Hiromu?SakuraiEmail author 《Journal of biological inorganic chemistry》2004,9(7):885-893
During the investigation of the development of insulin-mimetic zinc(II) complexes with a blood glucose-lowering effect in experimental diabetic animals, we found a potent bis(maltolato)zinc(II) complex, Zn(ma)2, exhibiting significant insulin-mimetic effects in a type 2 diabetic animal model. By using this Zn(ma)2 as the leading compound, we examined the in vitro and in vivo structure–activity relationships of Zn(ma)2 and its related complexes. The in vitro insulin-mimetic activity of these complexes was determined by the inhibition of free fatty acid release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine. A new Zn(II) complex with allixin isolated from garlic, Zn(alx)2, exhibited the highest insulin-mimetic activity among the complexes analyzed. The insulin-mimetic activity of the Zn(II) complexes examined strongly correlated (correlation coefficient=0.96) with the partition coefficient (logP) of the ligand, indicating that the activity of Zn(ma)2-related complexes depends on the lipophilicity of the ligand. The blood glucose-lowering effects of Zn(alx)2 and Zn(ma)2 were then compared, and both complexes were found to normalize hyperglycemia in KK-Ay mice after a 14-day course of daily intraperitoneal injections. However, Zn(alx)2 improved glucose tolerance in KK-Ay mice much more than did Zn(ma)2, indicating that Zn(alx)2 possesses greater in vivo anti-diabetic activity than Zn(ma)2. In addition, Zn(alx)2 improved leptin resistance and suppressed the progress of obesity in type 2 diabetic KK-Ay mice. On the basis of these observations, we conclude that the Zn(alx)2 complex is a novel potent candidate for the treatment of type 2 diabetes mellitus.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00775-004-0590-8 相似文献
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Suzuki Y Asano K Shiraishi Y Oguma T Shiomi T Fukunaga K Nakajima T Niimi K Yamaguchi K Ishizaka A 《Prostaglandins, leukotrienes, and essential fatty acids》2004,71(6):375-382
Thromboxane A2 receptor (TP) mediates bronchial smooth muscle cell (BSMC) contraction, airway hyperresponsiveness, and airway inflammation in patients with asthma. In the present study, a pathogenic role of TP activation in airway remodeling was examined using primary cultures of human BSMC. A TP agonist, I-BOP, concentration-dependently enhanced not only bromodeoxyuridine (BrdU) uptake but also cell proliferation of BSMC. A TP-selective antagonist, AA-2414, blocked the effects of I-BOP on both BrdU uptake and cell proliferation. I-BOP-induced BrdU uptake was significantly blocked by two non-selective tyrosine kinase inhibitors, genistein and herbimycin A, or a Src family tyrosine kinase inhibitor, PP2, but not by an inhibitor of epidermal growth factor (EGF) receptor-associated tyrosine kinase, AG1478. In conclusion, TP receptor activation causes DNA synthesis and cell proliferation of human BSMC by activating tyrosine kinases including Src, but not by EGF receptor transactivation. 相似文献
136.
Gu J Zhao Y Isaji T Shibukawa Y Ihara H Takahashi M Ikeda Y Miyoshi E Honke K Taniguchi N 《Glycobiology》2004,14(2):177-186
A rat pheochromocytoma cell line (PC12), when transfected with beta1,4-N-acetylglucosaminyltransferase III (GnT-III), which catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulted in the suppression of neurite outgrowth induced by costimulation of epidermal growth factor (EGF) and integrins. The neurite outgrowth was restored by the overexpression of a constitutively activated mitogen- or extracellular signal-regulated kinase kinase-1 (MEK-1). Consistent with this, the EGF receptor (EGFR)-mediated ERK activation was blocked in GnT-III transfectants. Conversely, the overexpression of dominant negative MEK-1 or treatment with PD98059, a specific inhibitor of MEK-1, inhibited neurite outgrowth in controls transfected with mock. Furthermore GnT-III activity is required for these inhibitions, because the overexpression of a dominant negative GnT-III mutant (D321A) failed to reduce neurite outgrowth and EGFR-mediated ERK activation. Lectin blot analysis confirmed that EGFR from wild-type GnT-III transfectants had been modified by bisecting GlcNAc in its N-glycan structures. This modification led to a significant decrease in EGF binding and EGFR autophosphorylation. Collectively, the results constitute a comprehensive body of evidence to show clearly that the overexpression of GnT-III prevents neurite outgrowth induced by costimulation of EGF and integrins through the Ras/MAPK activation pathway and indicates that GnT-III may be an important regulator for cell differentiation in neural tissues. 相似文献
137.
Identification of cold-inducible downstream genes of the Arabidopsis DREB1A/CBF3 transcriptional factor using two microarray systems 总被引:20,自引:0,他引:20
138.
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140.
Oku Y Ohtaki A Kamitori S Nakamura N Yohda M Ohno H Kawarabayasi Y 《Journal of inorganic biochemistry》2004,98(7):1194-1199
Cytochrome P450 from thermoacidophilic crenarchaeon, Sulfolobus tokodaii strain 7 (P450st) has been expressed in Escherichia coli and purified at high homogeneity. P450st was crystallized in an orthorhombic system with the space group P2(1)2(1)2(1) and cell dimensions of a=53.6 A, b=55.1 A, and c=130.9 A, and the structure was determined at a 3.0 A resolution. The final R-factor was 0.194 (Rfree=0.235). Structural comparison with cytochrome P450 from S. solfataricus (CYP119) suggests that the region composed of the F to G helices and the Cl- binding site is responsible for the affinity for a ligand coordinating heme iron. Direct electrochemistry of P450st in a didodecyldimethylammonium bromide (DDAB) film on a plastic formed carbon (PFC) electrode has also been demonstrated. A quasi-reversible redox response has been observed even at elevated temperatures of up to 80 degrees C. 相似文献