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41.
Yasuda S Wu PS Hattori E Tachibana H Yamada K 《Bioscience, biotechnology, and biochemistry》2004,68(1):51-58
A method for simultaneous detection and quantification is presented to determine the presence of isoflavones and bisphenol A in a biological sample. A coulometric array detector was used with reversed-phase high-performance liquid chromatography (HPLC). Daidzein (1), glycitein (2), genistein (3) and their glucoside conjugates, daidzin (4), glycitin (5) and genistin (6), were measured as phytochemicals. Also assayed here was equol (7), a metabolite from compound 1, and bisphenol A (8), an industrial chemical that acts as an endocrine disrupter. All chemicals were simultaneously detected by using a 600-mV single detection voltage with high efficacy. A mixture of 1, 3 and 8 was orally administered to rats, and the levels of these three chemicals in the serum were clearly increased after a 4 kU beta-glucuronidase treatment. The levels of compounds 1 and 3 in the serum were detected at 1665 and 2040 ng/ml, while 8 was at a low level of 417 ng/ml. Compound 7 in the serum was not detected until after enzymatic hydrolysis (72 ng/ml). These results suggest that this analytical method would be useful for metabolic and pharmacokinetic studies on isoflavones and bisphenol A. 相似文献
42.
Synergistic interaction of three ERECTA-family receptor-like kinases controls Arabidopsis organ growth and flower development by promoting cell proliferation 总被引:10,自引:0,他引:10
Growth of plant organs relies on coordinated cell proliferation followed by cell growth, but the nature of the cell-cell signal that specifies organ size remains elusive. The Arabidopsis receptor-like kinase (RLK) ERECTA regulates inflorescence architecture. Our previous study using a dominant-negative fragment of ERECTA revealed the presence of redundancy in the ERECTA-mediated signal transduction pathway. Here, we report that Arabidopsis ERL1 and ERL2, two functional paralogs of ERECTA, play redundant but unique roles in a part of the ERECTA signaling pathway, and that synergistic interaction of three ERECTA-family RLKs define aerial organ size. Although erl1 and erl2 mutations conferred no detectable phenotype, they enhanced erecta defects in a unique manner. Overlapping but distinct roles of ERL1 and ERL2 can be ascribed largely to their intricate expression patterns rather than their functions as receptor kinases. Loss of the entire ERECTA family genes led to striking dwarfism, reduced lateral organ size and abnormal flower development, including defects in petal polar expansion, carpel elongation, and anther and ovule differentiation. These defects are due to severely reduced cell proliferation. Our findings place ERECTA-family RLKs as redundant receptors that link cell proliferation to organ growth and patterning. 相似文献
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Nameki N Yoneyama M Koshiba S Tochio N Inoue M Seki E Matsuda T Tomo Y Harada T Saito K Kobayashi N Yabuki T Aoki M Nunokawa E Matsuda N Sakagami N Terada T Shirouzu M Yoshida M Hirota H Osanai T Tanaka A Arakawa T Carninci P Kawai J Hayashizaki Y Kinoshita K Güntert P Kigawa T Yokoyama S 《Protein science : a publication of the Protein Society》2004,13(8):2089-2100
GCN2 is the alpha-subunit of the only translation initiation factor (eIF2alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. In this study, we determined the solution structure of the mouse GCN2 RWD domain using NMR spectroscopy. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices, with an alphabetabetabetabetaalphaalpha topology. A characteristic YPXXXP motif, which always occurs in RWD domains, forms a stable loop including three consecutive beta-turns that overlap with each other by two residues (triple beta-turn). As putative binding sites with GCN1, a structure-based alignment allowed the identification of several surface residues in alpha-helix 3 that are characteristic of the GCN2 RWD domains. Despite the apparent absence of sequence similarity, the RWD structure significantly resembles that of ubiquitin-conjugating enzymes (E2s), with most of the structural differences in the region connecting beta-strand 4 and alpha-helix 3. The structural architecture, including the triple beta-turn, is fundamentally common among various RWD domains and E2s, but most of the surface residues on the structure vary. Thus, it appears that the RWD domain is a novel structural domain for protein-binding that plays specific roles in individual RWD-containing proteins. 相似文献
46.
Kubota NK Ohta E Ohta S Koizumi F Suzuki M Ichimura M Ikegami S 《Bioorganic & medicinal chemistry》2003,11(21):4569-4575
Piericidins C5 (1) and C6 (2), two new members of the piericidin family, were isolated from a Streptomyces sp. and a Nocardioides sp., together with known piericidins C1 (3), C2 (4), C3 (5), C4 (6), D1 (7), and A3 (8). The structures were determined on the basis of their spectroscopic data. Both new compounds inhibited cell division of fertilized starfish (Asterina pectinifera) eggs at the minimum inhibitory concentration of 0.09 microg/mL. 相似文献
47.
Hashimoto Y Tsuji O Niikura T Yamagishi Y Ishizaka M Kawasumi M Chiba T Kanekura K Yamada M Tsukamoto E Kouyama K Terashita K Aiso S Lin A Nishimoto I 《Journal of neurochemistry》2003,84(4):864-877
Amyloid precursor protein (APP), the precursor of Abeta, has been shown to function as a cell surface receptor that mediates neuronal cell death by anti-APP antibody. The c-Jun N-terminal kinase (JNK) can mediate various neurotoxic signals, including Abeta neurotoxicity. However, the relationship of APP-mediated neurotoxicity to JNK is not clear, partly because APP cytotoxicity is Abeta independent. Here we examined whether JNK is involved in APP-mediated neuronal cell death and found that: (i) neuronal cell death by antibody-bound APP was inhibited by dominant-negative JNK, JIP-1b and SP600125, the specific inhibitor of JNK, but not by SB203580 or PD98059; (ii) constitutively active (ca) JNK caused neuronal cell death and (iii) the pharmacological profile of caJNK-mediated cell death closely coincided with that of APP-mediated cell death. Pertussis toxin (PTX) suppressed APP-mediated cell death but not caJNK-induced cell death, which was suppressed by Humanin, a newly identified neuroprotective factor which inhibits APP-mediated cytotoxicity. In the presence of PTX, the PTX-resistant mutant of Galphao, but not that of Galphai, recovered the cytotoxic action of APP. These findings demonstrate that JNK is involved in APP-mediated neuronal cell death as a downstream signal transducer of Go. 相似文献
48.
All organisms face risks of unpredictable danger caused by harmful physical environments, pathogens, parasites or predators. Organisms may have several alternative ways of coping with such dangers. These differ in cost, effectiveness and activation time. We study the conditions under which it is optimal to use different alternatives for damage control. As an example we consider a microbe (such as E. coli), which may experience heat shocks that cause denaturation of proteins in the cell. To restore the denatured proteins the organism produces heat-shock proteins (HSP). There are two different pathways for production of HSP. Some HSP are produced immediately after a heat shock (feedforward control), but additional HSP may be produced thereafter, stimulated by the presence of denatured proteins (feedback control). Feedforward is based solely on heat-shock intensity without accurate information on the resulting amount of denatured proteins. We examine the optimal combination of the two pathways that minimizes the sum of the damage caused by the presence of untreated denatured proteins and the production cost of HSP. The optimal response depends on the time delay for feedback control, the effectiveness of HSP in processing denatured proteins, the production cost of HSP, the severity of damage by denatured proteins and the probability distribution of the abundance of denatured protein conditional on heat-shock intensity. We find that feedforward control should always be used. Additional HSP may be produced by feedback control when the abundance of denatured protein is large whilst no feedback control should be used when it is small. All the HSP are produced by feedforward control when the maximum is close to the mean of denatured protein abundance conditional on the heat-shock intensity. 相似文献
49.
Characterization of the unfolding process of lipocalin-type prostaglandin D synthase 总被引:6,自引:0,他引:6
Inui T Ohkubo T Emi M Irikura D Hayaishi O Urade Y 《The Journal of biological chemistry》2003,278(5):2845-2852
We found that low concentrations of guanidine hydrochloride (GdnHCl, <0.75 M) or urea (<1.5 M) enhanced the enzyme activity of lipocalin-type prostaglandin (PG) D synthase (L-PGDS) maximally 2.5- and 1.6-fold at 0.5 M GdnHCl and 1 M urea, respectively. The catalytic constants in the absence of denaturant and in the presence of 0.5 M GdnHCl or 1 m urea were 22, 57, and 30 min(-1), respectively, and the K(m) values for the substrate, PGH(2), were 2.8, 8.3, and 2.3 microm, respectively, suggesting that the increase in the catalytic constant was mainly responsible for the activation of L-PGDS. The intensity of the circular dichroism (CD) spectrum at 218 nm, reflecting the beta-sheet content, was also increased by either denaturant in a concentration-dependent manner, with the maximum at 0.5 M GdnHCl or 1 M urea. By plotting the enzyme activities against the ellipticities at 218 nm of the CD spectra of L-PGDS in the presence or absence of GdnHCl or urea, we found two states in the reversible folding process of L-PGDS: one is an activity-enhanced state and the other, an inactive state. The NMR analysis of L-PGDS revealed that the hydrogen-bond network was reorganized to be increased in the activity-enhanced state formed in the presence of 0.5 M GdnHCl or 1 m urea and to be decreased but still remain in the inactive intermediate observed in the presence of 2 M GdnHCl or 4 M urea. Furthermore, binding of the nonsubstrate ligands, bilirubin or 13-cis-retinal, to L-PGDS changed from a multistate mode in the native form of L-PGDS to a simple two-state mode in the activity-enhanced form, as monitored by CD spectra of the bound ligands. Therefore, L-PGDS is a unique protein whose enzyme activity and ligand-binding property are biphasically altered during the unfolding process by denaturants. 相似文献
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