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81.
Takahashi T Yamashita H Nagano Y Nakamura T Kohriyama T Matsumoto M 《FEBS letters》2006,580(18):4479-4484
Synphilin-1 is an alpha-synuclein binding protein that is involved in the pathogenesis of Parkinson's disease. The present study investigated the phospholipid-binding capacity of Synphilin-1. The C-terminus of Synphilin-1 was found to selectively bind to acidic phospholipids, including phosphatidic acid, phosphatidylserine, and phosphatidylglycerol, but not to naturally charged phospholipids. Synphilin-1 was targeted to cytoplasmic lipid droplets in mammalian cells. The amino acid sequence 610-640 was found to represent the primary determinant site for phospholipid binding. Moreover, the R621C mutation identified in Parkinson's disease abolished Synphilin-1 association with lipid droplets. The lipophilicity of Synphilin-1 might prove relevant to its physiologic function. 相似文献
82.
Modulation of functional properties of KCNQ1 channel by association of KCNE1 and KCNE2 总被引:1,自引:0,他引:1
Toyoda F Ueyama H Ding WG Matsuura H 《Biochemical and biophysical research communications》2006,344(3):814-820
The KCNE proteins (KCNE1 through KCNE5) function as beta-subunits of several voltage-gated K(+) channels. Assembly of KCNQ1 K(+) channel alpha-subunits and KCNE1 underlies cardiac I(Ks), while KCNQ1 interacts with all other members of KCNE forming complexes with different properties. Here we investigated synergic actions of KCNE1 and KCNE2 on functional properties of KCNQ1 heterologously expressed in COS7 cells. Patch-clamp recordings from cells expressing KCNQ1 and KCNE1 exhibited the slowly activating current, while co-expression of KCNQ1 with KCNE2 produced a practically time-independent current. When KCNQ1 was co-expressed with both of KCNE1 and KCNE2, the membrane current exhibited a voltage- and time-dependent current whose characteristics differed substantially from those of the KCNQ1/KCNE1 current. The KCNQ1/KCNE1/KCNE2 current had a more depolarized activation voltage, a faster deactivation kinetics, and a less sensitivity to activation by mefenamic acid. These results suggest that KCNE2 can functionally couple to KCNQ1 even in the presence of KCNE1. 相似文献
83.
84.
Seki N Toh U Kawaguchi K Ninomiya M Koketsu M Watanabe K Aoki M Fujii T Nakamura A Akagi Y Kusukawa J Kage M Shirouzu K Yamana H 《Journal of cellular biochemistry》2012,113(7):2346-2355
4',5,7-Trihydroxy-3',5'-dimethoxyflavone (Tricin), a naturally occurring flavone, has anti-inflammatory potential and exhibits diverse biological activities including antigrowth activity in several human cancer cell lines and cancer chemopreventive effects in the gastrointestinal tract of mice. The present study aimed to investigate the biological actions of tricin on hepatic stellate cells (HSCs) in vitro, exploring its potential as a treatment of liver fibrosis, since HSC proliferation is closely related to the progression of hepatic fibrogenesis in chronic liver diseases leading to irreversible liver cirrhosis and hepatocellular carcinoma. Tricin inhibited platelet-derived growth factor (PDGF)-BB-induced cell proliferation by blocking cell cycle progression and cell migration in the human HSC line LI90 and culture-activated HSCs. It also reduced the phosphorylation of PDGF receptor β and the downstream signaling molecules ERK1/2 and Akt, which might be due to its tyrosine kinase inhibitor properties rather than inhibition of the direct binding between PDGF-BB and its receptor. Our findings suggest that tricin might be beneficial in HSC-targeting therapeutic or chemopreventive applications for hepatic fibrosis. 相似文献
85.
DNA polymerase IV (Pol IV) is one of three translesion polymerases in Escherichia coli. A mass spectrometry study revealed that single-stranded DNA-binding protein (SSB) in lysates prepared from exponentially-growing cells has a strong affinity for column-immobilized Pol IV. We found that purified SSB binds directly to Pol IV in a pull-down assay, whereas SSBΔC8, a mutant protein lacking the C-terminal tail, failed to interact with Pol IV. These results show that the interaction between Pol IV and SSB is mediated by the C-terminal tail of SSB. When polymerase activity was tested on an SSBΔC8-coated template, we observed a strong inhibition of Pol IV activity. Competition experiments using a synthetic peptide containing the amino acid sequence of SSB tail revealed that the chain-elongating capacity of Pol IV was greatly impaired when the interaction between Pol IV and SSB tail was inhibited. These results demonstrate that Pol IV requires the interaction with the C-terminal tail of SSB to replicate DNA efficiently when the template ssDNA is covered with SSB. We speculate that at the primer/template junction, Pol IV interacts with the tail of the nearest SSB tetramer on the template, and that this interaction allows the polymerase to travel along the template while disassembling SSB. 相似文献
86.
A real-time PCR procedure targeting the gene of the molecular cochaperon DnaJ (dnaJ) was developed for specific detection of strains belonging to the Enterobacter cloacae group. The inclusivity and exclusivity of the real-time PCR assay were assessed with seven reference strains of E.?cloacae, 12 other Enterobacter species and 41 non-Enterobacter strains. Inclusivity as well as exclusivity of the duplex real-time PCR was 100%. In contrast, resolution of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was inadequate for delineation of Enterobacter asburiae, Enterobacter hormaechei, Enterobacter kobei and Enterobacter ludwigii from E.?cloacae. Eleven of 56 (20%) clinical isolates of the E.?cloacae group could not be clearly identified as a certain species using MALDI-TOF MS. In summary, the combination of MALDI-TOF MS with the E.?cloacae-specific duplex real-time PCR is an appropriate method for identification of the six species of the E.?cloacae complex. 相似文献
87.
Elizabeth A. Stoll Svetlana A. Mikheeva Richard P. Beyer David A. Plotnik Jeffrey L. Schwartz Jason K. Rockhill John R. Silber Donald E. Born Yoshito Kosai Philip J. Horner Robert C. Rostomily 《Aging cell》2012,11(6):1027-1035
Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3‐ and 18‐month‐old mice into 3‐ and 20‐month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ≤ 0.0001) median survival in both 3‐month (37.5 vs. 83 days) and 20‐month (38 vs. 67 days) hosts, indicating that age‐dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF‐1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age‐dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age‐dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas. 相似文献
88.
89.
Morita M Ishida N Uchiyama K Yamaguchi K Itoh Y Shichiri M Yoshida Y Hagihara Y Naito Y Yoshikawa T Niki E 《Free radical research》2012,46(6):758-765
An excessive accumulation of fat in the liver leads to chronic liver injury such as non-alcoholic fatty liver disease (NAFLD), which is an important medical problem affecting many populations worldwide. Oxidative stress has been implicated in the pathogenesis of NAFLD, but the exact nature of active species and the underlying mechanisms have not been elucidated. It was previously found that the administration of free radical-generating azo compound to mice induced accumulation of fat droplet in the liver. The present study was performed aiming at elucidating the changes of lipid classes and fatty acid composition and also measuring the levels of lipid peroxidation products in the liver induced by azo compound administration to mouse. The effects of azo compound on the liver were compared with those induced by high fat diet, a well-established cause of NAFLD. Azo compounds given to mice either by intraperitoneal administration or by dissolving to drinking water induced triacylglycerol (TG) increase and concomitant phospholipid decrease in the liver, whose pattern was quite similar to that induced by high fat diet. Lipid peroxidation products such as hydroxyoctadecadienoic acid and hydroxyeicosatetraenoic acid were increased in the liver in association with the increase in TG. These results show that free radicals as well as high fat diet induce fatty liver by similar mechanisms, in which lipid peroxidation may be involved. 相似文献
90.