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排序方式: 共有293条查询结果,搜索用时 187 毫秒
31.
Molecular Biology Reports - Previous studies have demonstrated that cytosolic phospholipase A2α (cPLA2α) is required for NOX2 NADPH oxidase activation in human and mouse phagocytes.... 相似文献
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Zanlin Yu Nurit Livnat-Levanon Oded Kleifeld Wissam Mansour Mark?A. Nakasone Carlos?A. Castaneda Emma?K. Dixon David Fushman Noa Reis Elah Pick Michael?H. Glickman 《Bioscience reports》2015,35(3)
26S proteasome, a major regulatory protease in eukaryotes, consists of a 20S proteolytic core particle (CP) capped by a 19S regulatory particle (RP). The 19S RP is divisible into base and lid sub-complexes. Even within the lid, subunits have been demarcated into two modules: module 1 (Rpn5, Rpn6, Rpn8, Rpn9 and Rpn11), which interacts with both CP and base sub-complexes and module 2 (Rpn3, Rpn7, Rpn12 and Rpn15) that is attached mainly to module 1. We now show that suppression of RPN11 expression halted lid assembly yet enabled the base and 20S CP to pre-assemble and form a base-CP. A key role for Regulatory particle non-ATPase 11 (Rpn11) in bridging lid module 1 and module 2 subunits together is inferred from observing defective proteasomes in rpn11–m1, a mutant expressing a truncated form of Rpn11 and displaying mitochondrial phenotypes. An incomplete lid made up of five module 1 subunits attached to base-CP was identified in proteasomes isolated from this mutant. Re-introducing the C-terminal portion of Rpn11 enabled recruitment of missing module 2 subunits. In vitro, module 1 was reconstituted stepwise, initiated by Rpn11–Rpn8 heterodimerization. Upon recruitment of Rpn6, the module 1 intermediate was competent to lock into base-CP and reconstitute an incomplete 26S proteasome. Thus, base-CP can serve as a platform for gradual incorporation of lid, along a proteasome assembly pathway. Identification of proteasome intermediates and reconstitution of minimal functional units should clarify aspects of the inner workings of this machine and how multiple catalytic processes are synchronized within the 26S proteasome holoenzymes. 相似文献
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Yoram Nevo Shlomit Aga-Mizrachi Edva Elmakayes Nurit Yanay Keren Ettinger Moran Elbaz Zivia Brunschwig Oshrat Dadush Galit Elad-Sfadia Roni Haklai Yoel Kloog Joab Chapman Shimon Reif 《PloS one》2011,6(3)
The Ras superfamily of guanosine-triphosphate (GTP)-binding proteins regulates a diverse spectrum of intracellular processes involved in inflammation and fibrosis. Farnesythiosalicylic acid (FTS) is a unique and potent Ras inhibitor which decreased inflammation and fibrosis in experimentally induced liver cirrhosis and ameliorated inflammatory processes in systemic lupus erythematosus, neuritis and nephritis animal models. FTS effect on Ras expression and activity, muscle strength and fibrosis was evaluated in the dy2J/dy2J mouse model of merosin deficient congenital muscular dystrophy. The dy2J/dy2J mice had significantly increased RAS expression and activity compared with the wild type mice. FTS treatment significantly decreased RAS expression and activity. In addition, phosphorylation of ERK, a Ras downstream protein, was significantly decreased following FTS treatment in the dy2J/dy2J mice. Clinically, FTS treated mice showed significant improvement in hind limb muscle strength measured by electronic grip strength meter. Significant reduction of fibrosis was demonstrated in the treated group by quantitative Sirius Red staining and lower muscle collagen content. FTS effect was associated with significantly inhibition of both MMP-2 and MMP-9 activities. We conclude that active RAS inhibition by FTS was associated with attenuated fibrosis and improved muscle strength in the dy2J/dy2J mouse model of congenital muscular dystrophy. 相似文献
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Roffman JL Nitenson AZ Agam Y Isom M Friedman JS Dyckman KA Brohawn DG Smoller JW Goff DC Manoach DS 《PloS one》2011,6(9):e25253
Background
Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.Methodology/Principal Findings
Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.Conclusions/Significance
These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene. 相似文献38.
Choe H Moore MJ Owens CM Wright PL Vasilieva N Li W Singh AP Shakri R Chitnis CE Farzan M 《Molecular microbiology》2005,55(5):1413-1422
Plasmodium vivax is one of four Plasmodium species that cause human malaria. P. vivax and a related simian malaria parasite, Plasmodium knowlesi, invade erythrocytes by binding the Duffy antigen/receptor for chemokines (DARC) through their respective Duffy binding proteins. Here we show that tyrosines 30 and 41 of DARC are modified by addition of sulphate groups, and that the sulphated tyrosine 41 is essential for association of the Duffy binding proteins of P. vivax (PvDBP) and P. knowlesi (PkDaBP) with DARC-expressing cells. These sulphated tyrosines also participate in the association of DARC with each of its four known chemokine ligands. Alteration of tyrosine 41 to phenylalanine interferes with MCP-1, RANTES and MGSA association with DARC, but not with that of IL8. In contrast, alteration of tyrosine 30 to phenylalanine interferes with the association of IL8 with DARC. A soluble sulphated amino-terminal domain of DARC, but not one modified to phenylalanine at residue 41, can be used to block the association of PvDBP and PkDaBP with red blood cells, with an IC50 of approximately 5 nM. These data are consistent with a role for tyrosine sulphation in the association of many or most chemokines with their receptors, and identify a key molecular determinant of erythrocyte invasion by P. vivax. 相似文献
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Lev EI Kornowski R Teplisky I Hasdai D Rechavia E Shor N Battler A Assali AR 《International journal of cardiovascular interventions》2005,7(1):41-45
The role of small molecules anti-glycoprotein (GP) IIb/IIIa pharmacotherapy during acute myocardial infarction (AMI) has not been established. The purpose of our study was to evaluate the clinical outcomes of patients sustaining AMI who underwent emergent percutaneous coronary intervention (PCI) and who were distinguished by the use of the anti-GP IIb/IIIa agent eptifibatide. We studied a consecutive group of 216 patients who underwent PCI for acute ST-elevation myocardial infarction and compared the outcomes of patients who received eptifibatide just prior and following the procedure (n=167) to those who were not on anti GP IIb/IIIa inhibitors (n=49). On average, patients treated using eptifibatide were younger and were more likely to be men, hypertensive, and smokers. The eptifibatide treated patients were less likely to have diabetes and renal failure and had worse angiographic characteristics. There were no significant differences between the groups in any of the clinical outcomes, including the composite endpoint (e.g. death, MI, repeat revascularization) and the rate of sub-acute stent thrombosis. Nonetheless, there was a non-significant trend towards lower 30 day mortality in the eptifibatide group (4.8% versus 12%, P=0.09). We concluded that in our comparative study of periprocedural administration of eptifibatide during emergent AMI angioplasty, there was a non-significant trend towards better short-term survival among eptifibatide treated patients although the composite endpoint did not differ between patients distinguished by the use of anti GP IIb/IIIa small molecule pharmacotherapy. 相似文献