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31.
Proprotein convertases regulate activity of prostate epithelial cell differentiation markers and are modulated in human prostate cancer cells 总被引:1,自引:0,他引:1
Uchida K Chaudhary LR Sugimura Y Adkisson HD Hruska KA 《Journal of cellular biochemistry》2003,88(2):394-399
Prostate derived factor (PDF) is a member of transforming growth factor-beta (TGF-beta) superfamily proteins involved in differentiation of the prostate epithelium. Proprotein convertases (PCs) such as furin are thought to mediate the processing of TGF-beta superfamily. In the present study, we demonstrated for the first time that human prostate cancer cell lines differentially synthesize and secret prostate derived factor (PDF), and that PDF secreted by LNCaP is processed by PCs. Exposure of LNCaP cells to the decanoyl-Arg-Val-Lys-Arg-chloromethylketone (CMK), a synthetic furin-like protease inhibitor, inhibited PDF processing and resulted in the loss of luminal cell phenotype and induction of basal cell phenotype in LNCaP cells as demonstrated by alternations in the expression of cytokeratins 8, 14, 18, and 19, markers of prostate epithelial cell differentiation. These results suggest that proprotein convertases may be involved in the regulation of prostate epithelial cell differentiation, and may be an important target of prostate cancer therapy. 相似文献
32.
M Terai C Furihata T Matsushima T Sugimura 《Archives of biochemistry and biophysics》1976,176(2):621-629
(i) Three forms of cyclic AMP phosphodiesterases (3′,5′-cyclic AMP 5′-nucleotidohydrolase, EC 3.1.4.17), F1, F2-I and F2-II, were partially purified from the soluble fraction of rat pancreas in the presence of excess protease inhibitors by DEAE-cellulose column chromatography and gel filtration and were characterized. (ii) F2-II, which was purified 31-fold, exhibited a single peak of activity on both polyacrylamide-gel electrophoresis and isoelectric focusing. The enzyme had a molecular weight of about 70,000, an isoelectric point of 3.9, and an optimal pH around 8.5 and required Mg2+ or Mn2+ but not Ca2+ for activity. The Km values of this enzyme for cyclic AMP and cyclic GMP were 1 and 50 μm, respectively, while V values of this enzyme for cyclic AMP and cyclic GMP were 36.1 and 12.6 nmol min?1 (mg of protein)?1, respectively. Cyclic GMP competitively inhibited hydrolysis of cyclic AMP by this enzyme. Ro20-1724 [4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone] also inhibited hydrolysis of cyclic AMP competitively, with a Ki value of 1 μm. (iii) Fraction F1, which was purified 10-fold, had a molecular weight of more than 500,000 and required Mg2+ for activity. Its Km values for cyclic AMP were 1 and 5 μm. Its Km value for cyclic GMP was 45 μm. Fraction F2-I, which was purified 26-fold, had a molecular weight of about 70,000. The ratio of the initial velocity of hydrolysis of cyclic GMP to that of cyclic AMP was 0.5 at a substrate concentration of 1 μm. 相似文献
33.
Arase S Ishii K Igarashi K Aisaki K Yoshio Y Matsushima A Shimohigashi Y Arima K Kanno J Sugimura Y 《Biology of reproduction》2011,84(4):734-742
The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). In the BPA-treated UGS, estradiol (E(2)) levels and CYP19A1 (cytochrome P450 aromatase) activity were significantly increased compared with those of the untreated and diethylstilbestrol (DES)-treated UGS. The mRNAs of steroidogenic enzymes, Cyp19a1 and Cyp11a1, and the sex-determining gene, Nr5a1, were up-regulated specifically in the BPA-treated group. The up-regulation of mRNAs was observed in the mesenchymal component of the UGS as well as in the cerebellum, heart, kidney, and ovary but not in the testis. The number of aromatase-expressing mesenchymal cells in the BPA-treated UGS was approximately twice that in the untreated and DES-treated UGS. The up-regulation of Esrrg mRNA was observed in organs for which mRNAs of steroidogenic enzymes were also up-regulated. We demonstrate here that fetal exposure to low-dose BPA has the unique action of increasing in situ E(2) levels and CYP19A1 (aromatase) activity in the mouse UGS. Our data suggest that BPA might interact with in situ steroidogenesis by altering tissue components, such as the accumulation of aromatase-expressing mesenchymal cells, in particular organs. 相似文献
34.
35.
K Yamashita A Umemoto S Grivas S Kato S Sato T Sugimura 《Nucleic acids symposium series》1988,(19):111-114
DNA adducts formed by 12 heterocyclic amines were analyzed by 32P-postlabeling method. Several DNA adducts were detected in rat liver by administration of each heterocyclic amine. Total adduct levels ranged from 0.5 for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to more than 250 for 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) per 10(7) nucleotides 24 hr after intragastric administration of these compounds. The N-hydroxy derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was reactive toward DNA in vitro to form adducts. Addition of acetic anhydride to N-OH-MeIQx greatly enhanced its reactivity to DNA. 32P-Postlabeling analysis revealed that the MeIQx-DNA adducts formed in vivo and in vitro were identical. Thus, MeIQx would be metabolized in vivo to N-hydroxy form and further esterified to produce more reactive species, such as N-acetoxy form, which modify DNA to form adducts. 相似文献
36.
The solvent effects of cyclopentyl methyl ether (CPME) on the reaction rates and enzyme enantioselectivity in the enantioselective transesterifications of racemic 6-methyl-5-hepten-2-ol (racemic sulcatol: SUL) and racemic 2,2-dimethyl-1,3-dioxolane-4-methanol (racemic solketal: SOL) with a series of enol esters catalyzed by Pseudomonas cepacia lipase co-lyophilized with cyclodextrins (-, -, -, partially methylated -,and 2,3,6-tri-O-methyl--cyclodextrin: CyD; CyD; CyD; Me1.78 CyD; Me3CyD) were investigated and compared with those in diisopropyl ether (IPE). In the case of SUL, enzyme activities of the co-lyophilizate with Me1.78 CyD in CPME were lower than those in IPE with every acyl source, however, the absolute enantiopreference was shown in the transesterification with vinyl butyrate (VBR) in IPME. When the substrates were SOL and VBR, the enzyme activities in CPME were greatly enhanced as high as 1.6–9.8-fold, while the enantioselectivities in CPME were comparable to those in IPE.Revisions requested 16 December 2004; Revisions received 17 January 2005 相似文献
37.
Formation and characterization of antibody against 2''-(5"-phosphoribosyl)-5'' AMP, the monomer form of poly(adenosine diphosphate ribose). 总被引:1,自引:0,他引:1 下载免费PDF全文
Specific antibody against 2'-(5"-phosphoribosyl)-5'AMP (PR-AMP), a monomer of poly(adenosine diphosphate ribose) (poly(ADP-Rib)), was produced by immunizing a rabbit with PR-AMP coupled to bovine serum albumin (BSA). Antibody against PR-AMP was purified 53-fold from serum by (NH4) 2SO4 precipitation, and BSA-Sepharose 4B, DEAE-cellulose and (PR-AMP)-BSA-Sepharose 4B column chromatographies. Inhibition experiments show that the adenine ring, 5'-phosphate residue and ribose-ribose bond of PR-AMP were essential for the antigenic determinant of PR-AMP. Anti PR-AMP antibody bound, not only with PR-AMP, but also with poly(ADP-Rib) of various chain lengths, while anti poly(ADP-Rib) antibody bound with poly(ADP-Rib) but not with PR-AMP. 相似文献
38.
39.
Koh N Fujimori T Nishiguchi S Tamori A Shiomi S Nakatani T Sugimura K Kishimoto T Kinoshita S Kuroki T Nabeshima Y 《Biochemical and biophysical research communications》2001,280(4):1015-1020
We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients. 相似文献
40.
Causal relationship between the loss of RUNX3 expression and gastric cancer 总被引:137,自引:0,他引:137
Li QL Ito K Sakakura C Fukamachi H Inoue Ki Chi XZ Lee KY Nomura S Lee CW Han SB Kim HM Kim WJ Yamamoto H Yamashita N Yano T Ikeda T Itohara S Inazawa J Abe T Hagiwara A Yamagishi H Ooe A Kaneda A Sugimura T Ushijima T Bae SC Ito Y 《Cell》2002,109(1):113-124
Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer. 相似文献