排序方式: 共有89条查询结果,搜索用时 31 毫秒
1.
Yu-Chi Su Goutham Venkata Naga Davuluri Cheng-Hao Chen Dong-Che Shiau Chien-Chin Chen Chia-Ling Chen Yee-Shin Lin Chih-Peng Chang 《PloS one》2016,11(2)
Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients. 相似文献
2.
Anupam Paliwal Alexis M. Temkin Kristi Kerkel Alexander Yale Iveta Yotova Natalia Drost Simon Lax Chia-Ling Nhan-Chang Charles Powell Alain Borczuk Abraham Aviv Ronald Wapner Xiaowei Chen Peter L. Nagy Nicholas Schork Catherine Do Ali Torkamani Benjamin Tycko 《PLoS genetics》2013,9(8)
Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM. 相似文献
3.
4.
5.
Sun HY Lin SW Ko TP Pan JF Liu CL Lin CN Wang AH Lin CH 《The Journal of biological chemistry》2007,282(13):9973-9982
Helicobacter pylori alpha1,3-fucosyltransferase (FucT) is involved in catalysis to produce the Lewis x trisaccharide, the major component of the bacteria's lipopolysaccharides, which has been suggested to mimic the surface sugars in gastric epithelium to escape host immune surveillance. We report here three x-ray crystal structures of FucT, including the FucT.GDP-fucose and FucT.GDP complexes. The protein structure is typical of the glycosyltransferase-B family despite little sequence homology. We identified a number of catalytically important residues, including Glu-95, which serves as the general base, and Glu-249, which stabilizes the developing oxonium ion during catalysis. The residues Arg-195, Tyr-246, Glu-249, and Lys-250 serve to interact with the donor substrate, GDP-fucose. Variations in the protein and ligand conformations, as well as a possible FucT dimer, were also observed. We propose a catalytic mechanism and a model of polysaccharide binding not only to explain the observed variations in H. pylori lipopolysaccharides, but also to facilitate the development of potent inhibitors. 相似文献
6.
7.
Calcium regulates the proliferation and differentiation of keratinocytes both in vivo and in vitro. Elevated extracellular Ca2+ concentration ([Ca2+]o) raises the intracellular free calcium ([Ca2+]i) and activates differentiation-related genes. Cells lacking the calcium-sensing receptor (CaR) fail to respond to [Ca2+]o and to differentiate, indicating a role for CaR in keratinocyte differentiation. These concepts derived from in vitro experiments have been tested and confirmed in two mouse models. 相似文献
8.
Hsing CH Lin MC Choi PC Huang WC Kai JI Tsai CC Cheng YL Hsieh CY Wang CY Chang YP Chen YH Chen CL Lin CF 《PloS one》2011,6(3):e17598
Background
Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages.Methodology/Principal Findings
Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages.Conclusions/Significance
These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways. 相似文献9.
Bcl-2 rescues ceramide- and etoposide-induced mitochondrial apoptosis through blockage of caspase-2 activation 总被引:5,自引:0,他引:5
Lin CF Chen CL Chang WT Jan MS Hsu LJ Wu RH Fang YT Tang MJ Chang WC Lin YS 《The Journal of biological chemistry》2005,280(25):23758-23765
Recent studies indicate that caspase-2 is involved in the early stage of apoptosis before mitochondrial damage. Although the activation of caspase-2 has been shown to occur in a large protein complex, the mechanisms of caspase-2 activation remain unclear. Here we report a regulatory role of Bcl-2 on caspase-2 upstream of mitochondria. Stress stimuli, including ceramide and etoposide, caused caspase-2 activation, mitochondrial damage followed by downstream caspase-9 and -3 activation, and cell apoptosis in human lung epithelial cell line A549. When A549 cells were pretreated with the caspase-2 inhibitor benzyloxycarbonyl-Val-Asp(-OMe)-Val-Ala-Asp(-OMe)-fluoromethyl ketone or transfected with caspase-2 short interfering RNA, both ceramide- and etoposide-induced mitochondrial damage and apoptosis were blocked. Overexpression of Bcl-2 prevented ceramide- and etoposide-induced caspase-2 activation and mitochondrial apoptosis. Furthermore, caspase-2 was activated when A549 cells were introduced with Bcl-2 short interfering RNA or were treated with Bcl-2 inhibitor, which provided direct evidence of a negative regulatory effect of Bcl-2 on caspase-2. Cell survival was observed when caspase-2 was inhibited in Bcl-2-silencing cells. Blockage of the mitochondrial permeability transition pore and caspase-9 demonstrated that Bcl-2-modulated caspase-2 activity occurred upstream of mitochondria. Further studies showed that Bcl-2 was dephosphorylated at serine 70 after ceramide and etoposide treatment. A protein phosphatase inhibitor, okadaic acid, rescued Bcl-2 dephosphorylation and blocked caspase-2 activation, mitochondrial damage, and cell death. Taken together, ceramide and etoposide induced mitochondria-mediated apoptosis by initiating caspase-2 activation, which was, at least in part, regulated by Bcl-2. 相似文献
10.
Yang HC Lin CH Hsu CL Hung SI Wu JY Pan WH Chen YT Fann CS 《Journal of biomedical science》2006,13(4):489-498
Summary Genetic dissection of complex diseases is both important and challenging. The human major histocompatibility complex is involved in many human diseases and genetic mechanisms. This highly polymorphic chromosome region has been extensively studied in Caucasians but not as well in Asians. Thus, we compared genotypic distributions, linkage disequilibria and haplotype blocks between Caucasian and Taiwan’s Han Chinese populations. Moreover, we investigated the population admixture and phylogenetic system in Han Chinese residing in Taiwan. The results show that Taiwan’s Han Chinese differ drastically in genotypic information compared with Caucasians but are relatively homogeneous among the three major ethnic subgroups, Minnan, Hakka and Mainlanders. Differences in allele frequency (AF) between Taiwanese and Caucasians in some disease-associated loci may reveal clues to differences in disease prevalence. The results of ethnic heterogeneity imply that public databases should be used with caution in cases where the study population(s) differs from the population characterized in the database. The high homogeneity we observed among the Taiwanese subpopulations mitigates the possibility of spurious association caused by ignoring population stratification in Taiwanese disease gene association studies. These results are useful for understanding our genetic background and designing future disease gene mapping studies.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献