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131.
Masayoshi Ichiba Yanping Wang Hirotaka Oishi Minako Lyadomi Naoko Shono Katsumaro Tomokuni 《Biomarkers》1996,1(3):211-214
Smoking-related aromatic DNA adducts in lymphocytes were measured from smokers (n = 76), ex-smokers (n = 25) and non-smokers (n = 56) by the 32P-postlabelling method, to clarify whether a genetic polymorphism for metabolic enzymes could explain the inter-individual variation of DNA adduct levels. Adduct levels were compared with respect to smoking status and polymorphic genotypes of cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GTSM1). The mean adduct level (1.24 per 108 nucleotides) in smokers was significantly higher than that (0.85 per 108) in non-smokers. Although we expected higher adduct levels in the CYP1A1 variant or GSTM1 null subjects, the adduct level in 'GSN1 nulls' was significantly lower than that in 'GSTM1 presents' among smokers. DNA adduct levels had significant positive correlations with smoking indices such as number of cigarettes or smoking years in all subjects. In smokers only, however, no correlation was found, because there were negative correlations between adduct levels and smoking dose in GSTM1 null genotypes. CYP1A1 genotypes had no effects on adduct levels. 相似文献
132.
Shimizu T Yamanaka Y Nojima H Yabe T Hibi M Hirano T 《Mechanisms of development》2002,110(1-2):125-138
To gain insight into the genetic mechanisms of photoreceptor development, we analyzed a collection of zebrafish mutations characterized by early photoreceptor cell loss. The mutant defects impair outer segment formation and are accompanied by an abnormal distribution of visual pigments. Rods and different cone types display defects of similar severity suggesting that genetic pathways common to all photoreceptors are affected. To investigate whether these phenotypes involve cell–cell interaction defects, we analyzed genetically mosaic animals. Interaction of niezerka photoreceptors with wild-type tissues improves the survival of mutant cells and restores their elongated morphology. In contrast, cells carrying mutations in the loci brudas, elipsa, fleer, and oval retain their defective phenotypes in a wild-type environment indicating cell-autonomy. These experiments identify distinct phenotypic categories of photoreceptor mutants and indicate that zebrafish photoreceptor defects involve both cell-autonomous and cell-nonautonomous mechanisms. 相似文献
133.
Wu ZL Zhang L Yabe T Kuberan B Beeler DL Love A Rosenberg RD 《The Journal of biological chemistry》2003,278(19):17121-17129
Fibroblast growth factor (FGF) signaling begins with the formation of a ternary complex of FGF, FGF receptor (FGFR), and heparan sulfate (HS). Multiple models have been proposed for the ternary complex. However, major discrepancies exist among those models, and none of these models have evaluated the functional importance of the interacting regions on the HS chains. To resolve the discrepancies, we measured the size and molar ratio of HS in the complex and showed that both FGF1 and FGFR1 simultaneously interact with HS; therefore, a model of 2:2:2 FGF1.HS.FGFR1 was shown to fit the data. Using genetic and biochemical methods, we generated HSs that were defective in FGF1 and/or FGFR1 binding but could form the signaling ternary complex. Both genetically and chemically modified HSs were subsequently assessed in a BaF3 cell mitogenic activity assay. The ability of HS to support the ternary complex formation was found to be required for FGF1-stimulated cell proliferation. Our data also proved that specific critical groups and sites on HS support complex formation. Furthermore, the molar ratio of HS, FGF1, and FGFR1 in the ternary complex was found to be independent of the size of HS, which indicates that the selected model can take place on the cell surface proteoglycans. Finally, a mechanism for the FGF.FGFR signaling complex formation on cell membrane was proposed, where FGF and FGFR have their own binding sites on HS and a distinct ternary complex formation site is directly responsible for mitogenic activity. 相似文献
134.
135.
Akira Tomokuni Hidetoshi Eguchi Yoshito Tomimaru Hiroshi Wada Koichi Kawamoto Shogo Kobayashi Shigeru Marubashi Masahiro Tanemura Hiroaki Nagano Masaki Mori Yuichiro Doki 《Biochemical and biophysical research communications》2011,(4):675
Background
Interferon-based (IFN-based) therapy is effective in the treatment of advanced hepatocellular carcinoma (HCC). However, the issue of resistance to this therapy remains to be solved. The aim of this study was to identify microRNAs (miRNAs) that govern the sensitivity to IFN-α in HCC cells.Methods
miRNA microarray analysis using IFN-α-resistant clones of PLC/PRF/5 (PLC-Rs) and their parental cells (PLC-P) was conducted. Changes in the anti-cancer effects of IFN-α were studied after gain-of-function and loss-of-function of the candidate miRNA.Results
miR-146a expression was significantly higher in PLC-Rs than in PLC-P. miR-146a decreased the sensitivity to IFN-α through the suppression of apoptosis. Further experiments showed that miR-146a-related resistance to IFN-α was mediated through SMAD4.Conclusions
The results indicated that miR-146a regulated the sensitivity of HCC cells to the cytotoxic effects of IFN-α through SMAD4, suggesting that this miRNA could be suitable for prediction of the clinical response and potential therapeutic target in HCC patients on IFN-based therapy. 相似文献136.
137.
138.
Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. 下载免费PDF全文
A reaction sequence, norsolorinic acid (NA)-->averantin (AVN)-->5'-hydroxyaverantin (HAVN)-->averufin (AVR), is the early part of a biosynthetic pathway for aflatoxins. In this study, we determined the stereochemical relationship among these metabolites by using chiral high-performance liquid chromatography. In cell-free experiments using the cytosol fraction of Aspergillus parasiticus NIAH-26, (1'S)-AVN was exclusively produced from NA in the presence of NADPH. Also, only (1'S)-AVN, and not (1'R)-AVN, served as a substrate for the reverse reaction from AVN to NA. When the microsome fraction of NIAH-26 was incubated with (1'S)-AVN in the presence of NADPH, two HAVN diastereomers and one AVR enantiomer were formed, whereas these substances were never produced from (1'R)-AVN. Moreover, (1'S,5'R)-AVR was exclusively formed from both HAVN diastereomers by the cytosol fraction in the presence of NAD. The feeding experiments using this mutant showed that aflatoxins were produced from (1'S,5'R)-AVR but not from (1'R,5'S)-AVR. These results indicate that the enzymes involved in this pathway show strict stereospecificity to their substrates and that the configuration of (1'S,5'R)-AVR leading to the formation of aflatoxins is due to the stereospecificity of NA dehydrogenase which catalyzes the reaction between (1'S)-AVN and NA. 相似文献
139.
Noritsugu Yabe Yasuharu Itagaki Morimasa Tanimoto Hisao Matsui 《Biotechnology letters》2000,22(22):1767-1773
Conditioned culture medium of rat small intestinal epithelial cells suppressed proliferation of spleen lymphocytes stimulated with concanavalin A (approx. 10% of its control [3H]thymidine incorporation) whereas conditioned phosphate-buffered saline of the epithelial cells did not. On the other hand, conditioned saline of the epithelial cells exposed to a mixture of total 22 amino acids at their concentrations in the culture medium suppressed the proliferation (approx. 45% of its control [3H]thymidine incorporation). Neither conditioned saline of the epithelial cells exposed to other medium components nor lysates of freshly harvested epithelial cells suppressed the proliferation. Thus, amino acids synergistically stimulated intestinal epithelial cells to produce substances with the ability to suppress lymphocyte proliferation. 相似文献
140.
Barbels of the Mullidae and Polymixiidae were observed osteologically and myologically. They were considered to be derived
from branchiostegal rays. Four muscles, the extensor tentaculi, retractor tentaculi, and two sections of rotator tentaculi,
were related to the barbels in both families. These muscles originate from almost all the hyoid bones in mullids, whereas
they originate only from the ventral hypohyal and fifth branchiostegal ray in polymixiids. In addition, each muscle related
to the barbel of the former is independent from others, but that of the latter is interconnected. These muscular differences
indicate that the barbels occurring in the two families are nonhomologous.
Received: August 27, 2000 / Revised: April 11, 2001/ Accepted: May 13, 2001 相似文献