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241.
Dong Gao Ruipeng Wang Bingfeng Li Yongkang Yang Zhonghe Zhai Dan-Ying Chen 《Cellular and molecular life sciences : CMLS》2009,66(15):2573-2584
Toll-like receptors (TLRs) act as sensors of microbial components and elicit innate immune responses. All TLR signaling pathways
activate the nuclear factor-kappaB (NF-κB), which controls the expression of inflammatory cytokine genes. Transforming growth
factor-β-activated kinase 1 (TAK1) is a serine/threonine protein kinase that is critically involved in the activation of NF-κB
by tumor necrosis factor (TNFα), interleukin-1β (IL-1β) and TLR ligands. In this study, we identified a novel protein, WD40
domain repeat protein 34 (WDR34) as a TAK1-interacting protein in yeast two-hybrid screens. WDR34 interacted with TAK1, TAK1-binding
protein 2 (TAB2), TAK1-binding protein 3 (TAB3) and tumor necrosis factor receptor-associated factor 6 (TRAF6) in overexpression
and under physiological conditions. Overexpression of WDR34 inhibited IL-1β-, polyI:C- and lipopolysaccharide (LPS)-induced
but not TNFα-induced NF-κB activation, whereas knockdown of WDR34 by a RNA-interference construct potentiated NF-κB activation
by these ligands. Our findings suggest that WDR34 is a TAK1-associated inhibitor of the IL-1R/TLR3/TLR4-induced NF-κB activation
pathway.
D. Gao and R. Wang contributed equally to this work. 相似文献
242.
Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to
be defined. ApoM (25 kDa) has a typical lipocalin ?-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low
affinity and may not be the natural ligands. ApoM retains its signal peptide, which serves as a hydrophobic anchor to the
lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma
(1 μM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol metabolism.
However, in casecontrol studies, apoM levels in patients with coronary heart disease (CHD) and controls were similar, suggesting
apoM levels not to affect the risk for CHD in humans. Experiments in transgenic mice suggested apoM to have antiatherogenic
properties; possible mechanisms include increased formation of pre-? HDL, enhanced cholesterol mobilization from foam cells,
and increased antioxidant properties.
Received 28 November 2008; received after revision 15 December 2008; accepted 16 December 2008 相似文献
243.
V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
244.
利用化学偶联法,将8种不同性质的高分子微球与自制的兔免疫球蛋白偶联,根据偶联量大小,考虑微球的性价比,选择出合适的高分子微球产品.实验对200目的氨基硅胶微球的偶联条件作进一步摸索.结果表明,当偶联时间6~8 h,EDC浓度10 g/L,反应pH为5.0,温度为4℃,蛋白质初始浓度为0.7 g/L时,兔免疫球蛋白的偶联量达到6 mg蛋白/g微球,黄曲酶毒素B1的柱回收率在90%以上,达到放大生产要求. 相似文献
245.
从影响融合率的2个主要因素探讨骨髓瘤细胞系Sp2/0细胞与黄曲霉毒素B_1免疫的脾细胞融合的最佳条件,使融合率达到100%.经筛选和克隆化,获得3株稳定分泌单克隆抗体的细胞株,分别命名为3B3、3H9、5G9.经过鉴定3株均为IgG_1亚类.其中3B3抗体与其他黄曲霉毒素几乎不发生交叉反应,腹水效价为1∶2×10~5,亲和力常数为3.1×10~7 L/mol,竞争性ELISA测出3B3抗体的最低反应浓度为0.05μg/L标准AFB_1样品的的回收率达96%.另外两株腹水抗体水平低,交叉反应强烈,腹水效价仅在1∶10~4数量级. 相似文献
246.
利用紫外线对克雷伯杆菌进行诱变,筛选出耐高浓度甘油且1,3-丙二醇(1,3-PD)产量较高的突变株KpⅥ.实验结果表明,在距离34 cm,功率30 W的紫外灯垂直照射下,最佳紫外诱变时间为6 min,此时,致死率为90.9%.克雷伯杆菌经过紫外诱变后,菌落明显增大,是原始菌株的2~4倍;变异菌株KpⅥ经过6代遗传稳定性考察,甘油消耗率和1,3-PD产量稳定,且保持了较高水平.在甘油质量浓度为90 g.L-1的条件下,变异菌株KpⅥ的甘油消耗率为98.3%,甘油转化率为50.4%,1,3-PD产量为44.81 g.L-1,生产能力达到0.75 g.(L.h)-1. 相似文献
247.
248.
Selenium is an essential trace element. In cattle, selenium deficiency causes dysfunction of various organs, including skeletal
and cardiac muscles. In humans as well, lack of selenium is associated with many disorders, but despite accumulation of clinical
reports, muscle diseases are not generally considered on the list. The goal of this review is to establish the connection
between clinical observations and the most recent advances obtained in selenium biology. Recent results about a possible role
of selenium-containing proteins in muscle formation and repair have been collected. Selenoprotein N is the first selenoprotein
linked to genetic disorders consisting of different forms of congenital muscular dystrophies. Understanding the muscle disorders
associated with selenium deficiency or selenoprotein N dysfunction is an essential step in defining the causes of the disease
and obtaining a better comprehension of the mechanisms involved in muscle formation and maintenance.
Received 13 July 2005; received after revision 9 September 2005; accepted 4 October 2005 相似文献
249.
Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered
in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin
genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the
expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships
with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process,
the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong
oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely
licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign
antigens in some autoimmune and allergic diseases.
Received 25 October 2007; accepted 12 December 2007 相似文献
250.