FEBS Letters
0014-5793
Cơ quản chủ quản: WILEY , Wiley-Blackwell
Lĩnh vực:
Molecular BiologyBiochemistryBiophysicsGeneticsCell BiologyStructural Biology
Các bài báo tiêu biểu
ERβ: Identification and characterization of a novel human estrogen receptor A novel estrogen receptor (hereinafter referred to as ERβ) was cloned using degenerate PCR primers. A comparison of the amino acid sequence of ERβ with the ‘classical’ ER (ERα) shows a high degree of conservation of the DNA‐binding domain (96%), and of the ligand‐binding domain (58%). In contrast, the A/B domain, the hinge region and the F‐domain are not conserved. Northern blot analysis revealed that ERβ is expressed in human thymus, spleen, ovary and testis. Transient transfections of an ERβ expression construct together with an ERE‐based reporter construct in CHO cells clearly demonstrated transactivation of ERβ by 17β‐estradiol. In addition, the ERα antagonist ICI‐164384 is a potent antagonist for ERβ as well. Interestingly, the level of transactivation by 17β‐estradiol is higher for ERα than for ERβ, which may reflect suboptimal conditions for ERβ at the level of the ligand, responsive element or cellular context.
Tập 392 Số 1 - Trang 49-53 - 1996
SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1 A class of pyridinyl imidazoles inhibit the MAP kinase homologue, termed here reactivating kinase (RK) [Lee et al. (1994) Nature 372, 739–746]. We now show that one of these compounds (SB 203580) inhibits RK in vitro (IC50 = 0.6 μM), suppresses the activation of MAPKAP kinase‐2 and prevents the phosphorylation of heat shock protein (HSP) 27 in response to interleukin‐1, cellular stresses and bacterial endotoxin in vivo. These results establish that MAPKAP kinase‐2 is a physiological RK substrate, and that HSP27 is phosphorylated by MAPKAP kinase‐2 in vivo. The specificity of SB 203580 was indicated by its failure to inhibit 12 other protein kinases in vitro, and by its lack of effect on the activation of RK kinase and other MAP kinase cascades in vivo. We suggest that SB 203580 will be useful for identifying other physiological roles and targets of RK and MAPKAP kinase‐2.
Tập 364 Số 2 - Trang 229-233 - 1995
High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria Formation of H2 O2 has been studied in rat heart mitochondria, pretreated with H2 O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2 O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2 O2 production. Inhibition of H2 O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the ΔΨ decrease by these compounds. A threshold ΔΨ value is found, above which a very strong increase in H2 O2 production takes place. This threshold slightly exceeds the state 3 ΔΨ level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169–202] that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.
Tập 416 Số 1 - Trang 15-18 - 1997
Cyanobacterial microcystin‐LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants The cyclic heptapeptide, microcystin‐LR, inhibits protein phosphatases 1 (PP1) and 2A (PP2A) with K
i , values below 0.1 nM. Protein phosphatase 2B is inhibited 1000‐fold less potently, while six other phosphatases and eight protein kinases tested are unaffected. These results are strikingly similar to those obtained with the tumour promoter okadaic acid. We establish that okadaic acid prevents the binding of microcystin‐LR to PP2A, and that protein inhibitors 1 and 2 prevent the binding of microcystin‐LR to PP1. We discuss the possibility that inhibition of PP1 and PP2A accounts for the extreme toxicity of microcystin‐LR, and indicate its potential value in the detection and analysis of protein kinases and phosphatases.
Tập 264 Số 2 - Trang 187-192 - 1990
LEAP‐1, a novel highly disulfide‐bonded human peptide, exhibits antimicrobial activity We report the isolation and characterization of a novel human peptide with antimicrobial activity, termed LEAP‐1 (liver‐expressed antimicrobial peptide). Using a mass spectrometric assay detecting cysteine‐rich peptides, a 25‐residue peptide containing four disulfide bonds was identified in human blood ultrafiltrate. LEAP‐1 expression was predominantly detected in the liver, and, to a much lower extent, in the heart. In radial diffusion assays, Gram‐positive Bacillus megaterium , Bacillus subtilis , Micrococcus luteus , Staphylococcus carnosus , and Gram‐negative Neisseria cinerea as well as the yeast Saccharomyces cerevisiae dose‐dependently exhibited sensitivity upon treatment with synthetic LEAP‐1. The discovery of LEAP‐1 extends the known families of mammalian peptides with antimicrobial activity by its novel disulfide motif and distinct expression pattern.
Tập 480 Số 2-3 - Trang 147-150 - 2000
Uncoupling protein‐3: a new member of the mitochondrial carrier family with tissue‐specific expression Brown adipose tissue (BAT) and skeletal muscle are important sites of nonshivering thermogenesis. The uncoupling protein‐1 (UCP1) is the main effector of nonshivering thermogenesis in BAT and the recently described ubiquitous UCP2 [1] has been implicated in energy balance. In an attempt to better understand the biochemical events underlying nonshivering thermogenesis in muscle, we screened a human skeletal muscle cDNA library and isolated three clones: UCP2, UCP3L and UCP3S . The novel UCP3 was 57% and 73% identical to human UCP1 and UCP2, respectively, highly skeletal muscle‐specific and its expression was unaffected by cold acclimation. This new member of the UCP family is a candidate protein for the modulation of the respiratory control in skeletal muscle.
Tập 408 Số 1 - Trang 39-42 - 1997
Identification of two distinct synucleins from human brain Two abundant proteins of 140 and 134 amino acids were purified and sequenced from human brain. They were identified through their reactivity on immunoblots with a partially characterised monoclonal antibody that recognises tau protein in a phosphorylation‐dependent manner. The 140 amino acid protein is identical with the precursor of the non‐Aβ component of Alzheimer's disease amyloid which in turn is highly homologous to synuclein from Torpedo electroplaques and rat brain. The 134 amino acid protein is the human homologue of bovine phosphoneuroprotein 14; it is 61% identical in sequence to the 140 amino acid protein. The previously unrecognised homology between these two proteins defines a family of human brain synucleins. We refer to the 140 and 134 amino acid proteins as α‐synuclein and β‐synuclein, respectively. Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals.
Tập 345 Số 1 - Trang 27-32 - 1994
Antioxidant activities of carotenes and xanthophylls The purpose of this study was to assess the relative antioxidant activities of a range of carotenes and xanthophylls through the extent of their abilities to scavenge the ABTS·+ radical cation. The results show that the relative abilities of the carotenoids to scavenge the ABTS·+ radical cation are influenced by the presence of functional groups with increasing polarities, such as carbonyl and hydroxyl groups, in the terminal rings, as well as by the number of conjugated double bonds.
Tập 384 Số 3 - Trang 240-242 - 1996
Enhanced autoradiographic detection of <sup>32</sup>P and <sup>125</sup>I using intensifying screens and hypersensitized film
Tập 82 Số 2 - Trang 314-316 - 1977
Interleukin‐8, a chemotactic and inflammatory cytokine Interleukin‐8 (IL‐8) belongs to a family of small, structurally related cytokines similar to platelet factor 4. It is produced by phagocytes and mesenchymal cells exposed to inflammatory stimuli (e.g., interleukin‐1 or tumor necrosis factor) and activates neutrophils inducing, chemotaxis, exocytosis and the respiratory burst. In vivo, IL‐8 elicits a massive neutrophil accumulation at the site of injection. Five neutrophil‐activating cytokines similar to IL‐8 in structure and function have been identified recently. IL‐8 and the related cytokines are produced in several tissues upon infection, inflammation, ischemia, trauma etc., and are thought to be the main cause of local noutrophil accumulation.
Tập 307 Số 1 - Trang 97-101 - 1992