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551.
Gil Mor Mariel Eliza Joon Song Brinda Wiita Shiuan Chen Frederick Naftolin 《The Journal of steroid biochemistry and molecular biology》2001,79(1-5)
17α-Methyl testosterone is a synthetic androgen with affinity for the androgen receptor. 17α-Methyl testosterone is used widely as a component of hormone replacement therapy. Previous reports have indicated that contrary to testosterone, 17α-methyl testosterone is not aromatized. However, 17α-methyl testosterone still could affect local estrogen formation by regulating aromatase expression or by inhibiting aromatase action. Both possibilities have important clinical implications. To evaluate the effect of 17α-methyl testosterone on the expression and activity of aromatase, we tested the choriocarcinoma Jar cell line, a cell line that express high levels of P450 aromatase, and the macrophage-like THP-1 cells, which express aromatase only after undergoing differentiation. We found that in both cell lines, 17α-methyl testosterone inhibits aromatase activity in a dose-related manner. The curve of inhibition parallels that of letrozole and gives complete inhibition at 10−4 M 17α-methyl testosterone, determined by the tritium release assay. 17α-Methyl testosterone does not have detectable effects on aromatase RNA and protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase activity and showed no effect of 17α-methyl testosterone, but differentiated THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by 17α-methyl testosterone to that seen in Jar cells. The Lineweaver–Burke plot shows 17α-methyl testosterone to be a competitive aromatase inhibitor. Our results show for the first time that 17α-methyl testosterone acts as an aromatase inhibitor. These findings are relevant for understanding the effects of 17α-methyl testosterone as a component of hormone replacement therapy. 17α-Methyl testosterone may, as a functional androgen and orally active steroidal inhibitor of endogenous estrogen production, also offer special possibilities for the prevention/treatment of hormone-sensitive cancers. 相似文献
552.
耐盐及苯乙酸、甲基对硫磷降解基因工程菌的构建 总被引:10,自引:1,他引:9
H1(Halomonas sp.)是一株耐高盐浓度(18% NaCl, W/V)和降解苯乙酸的菌株,pDT3质粒为pUC19插入甲基对硫磷水解酶基因(mpd基因)构建而成。采用HindⅢ酶切,获得含有完整mpd基因片段,克隆到广宿主质粒pKT230和pBBR1MCS2上,构建成质粒pKTMP和pBBRMP。通过三亲杂交,在辅助质粒pRK2013的帮助下,将质粒pKTMP和pBBRMP转移到H1中,得到的工程菌HpKTMP和HpBBRMP具有耐盐、降解苯乙酸和水解甲基对硫磷的功能,其中HpBBRMP水解酶活性与亲本菌株甲基对硫磷降解菌(Pseudomonas putida)DLLE4相当,而HpKTMP水解酶活性要提高1倍左右。经过传代试验,证明了工程菌的稳定性。 相似文献
553.
The limonoid derivative, methyl uguenenoate, the azole, uguenenazole, and the amide, uguenenonamide, together with the known furoquinoline alkaloids flindersiamine and maculosidine, and syringaldehyde have been isolated from the root of the East African Rutaceae Vepris uguenensis. While methyl uguenenoate and the furoquinoline alkaloids displayed mild antimalarial activity, the azole and amide were completely inactive. 相似文献
554.
555.
556.
Improvements to phosphopeptide enrichment protocols employing titanium dioxide (TiO2) are described and applied to identification of phosphorylation sites on recombinant human cyclin-dependent kinase 2 (CDK2). Titanium dioxide binds phosphopeptides under acidic conditions, and they can be eluted under basic conditions. However, some nonphosphorylated peptides, particularly acidic peptides, bind and elute under these conditions as well. These nonphosphorylated peptides contribute significantly to ion suppression of phosphopeptides and also increase sample complexity. We show here that the conversion of peptide carboxylates to their corresponding methyl esters sharply reduces nonspecific binding, improving the selectivity for phosphopeptides, just as has been reported for immobilized metal affinity chromatography (IMAC) columns. We also present evidence that monophosphorylated peptides can be effectively fractionated from multiply phosphorylated peptides, as well as acidic peptides, via stepwise elution from TiO2 using pH step gradients from pH 8.5 to pH 11.5. These approaches were applied to human CDK2 phosphorylated in vitro by yeast CAK1p in the absence of cyclin. We confirmed phosphorylation at T160, a site previously documented and shown to be necessary for CDK2 activity. However, we also discovered several novel sites of partial phosphorylation at S46, T47, T165, and Y168 when ion-suppressing nonphosphorylated peptides were eliminated using the new protocols. 相似文献
557.
Kotabová E Kana R Kyseláková H Lípová L Novák O Ilík P 《Journal of plant physiology》2008,165(15):1563-1571
Light-induced deepoxidation of violaxanthin to antheraxanthin and zeaxanthin in plants is associated with the induction of pronounced xanthophyll-dependent non-photochemical quenching (NPQ). To date, a misbalance between a high amount of zeaxanthin in thylakoid membranes and low NPQ has been explained by an absence of lumen acidification (e.g. when NPQ is measured in the dark after high light stress). In this study, we report that this misbalance can also be observed under moderate light. We found this result (deepoxidation state, DEPS, above 55% and NPQ0.9) in barley leaves treated with 10 μM methyl viologen (MV) under white light (100 μmol photons m−2 s−1, photosynthetically active radiation (PAR), growth irradiance). The addition of MV at this moderate light did not accelerate electron transport in thylakoid membranes, and induced only slight oxidative stress (no lipid peroxidation, almost unchanged maximum yield of photosystem II photochemistry, a decrease in activity of ascorbate peroxidase, and an increase in that of glutathion reductase). We suggest that, in leaves treated under the conditions used here, the lumen acidification induced by light-limited electron transport in thylakoid membranes was high enough to activate violaxanthin deepoxidase, but not sufficiently high to form the expected number of zeaxanthin-dependent quenching centers in photosystem II antennae. 相似文献
558.
Yao H Gong Y Zuo K Ling H Qiu C Zhang F Wang Y Pi Y Liu X Sun X Tang K 《Journal of plant physiology》2008,165(2):203-213
As the second enzyme of the non-mevalonate terpenoid pathway for isopentenyl diphosphate biosynthesis, DXP reductoisomerase (DXR, EC: 1.1.1.267) catalyzes a committed step of the MEP pathway for camptothecin (CPT) biosynthesis. In order to understand more about the role of DXR involved in the CPT biosynthesis at the molecular level, the full-length DXR cDNA sequence (designated as CaDXR) was isolated and characterized for the first time from a medicinal Nyssaceae plant species, Camptotheca acuminata. The full-length cDNA of CaDXR was 1823 bp containing a 1416 bp open reading frame (ORF) encoding a polypeptide of 472 amino acids. Comparative and bioinformatic analyses revealed that CaDXR showed extensive homology with DXRs from other plant species and contained a conserved transit peptide for plastids, an extended Pro-rich region and a highly conserved NADPH binding motif in its N-terminal region owned by all plant DXRs. Phylogenetic analysis indicated that CaDXR was more ancient than other plant DXRs. Tissue expression pattern analysis revealed that CaDXR expressed strongly in stem, weak in leaf and root. CaDXR was found to be an elicitor-responsive gene, which could be induced by exogenous elicitor of methyl jasmonate. The functional color complementation assay indicated that CaDXR could accelerate the biosynthesis of carotenoids in the Escherichia coli transformant, demonstrating that DXP reductoisomerase plays an influential step in isoprenoid biosynthesis. 相似文献
559.
超高产水稻组合‘培矮64S/E32’的耐光氧化特性及其机理 总被引:3,自引:0,他引:3
甲基紫精(MV)介导的光氧化导致两个水稻品种‘汕优63’(目前我国大面积推广的杂交水稻)和‘培矮64S/E32’(新培育的超高产杂交水稻)细胞电解质渗漏率都增加,前者增加的量大于后者,显示‘培矮64S/E32’的细胞膜系统受光氧化的伤害小。光氧化条件下,‘培矮64S/E32’仍能维持较高的光合放氧能力(Amax,φi)、PSⅡ活性(Fv/Fm、φPSⅡ)和叶绿素荧光猝灭系数(qP、MPQ),而且光氧化引起‘培矮64S/E32’这些参数的下降幅度也小。另外,光氧化导致了两个水稻品种抗氧化酶SOD和APX活性增加,‘培矮64S/E32’增加的幅度约为‘汕优63’的3倍。结果 表明超高产水稻具有更强的耐光氧化能力。 相似文献
560.
Treatment of cells with genotoxic agents affects protein degradation in both positive and negative ways. Exposure of S. cerevisiae to the alkylating agent MMS resulted in activation of genes that are involved in ubiquitin- and 26S proteasome-dependent protein degradation. This process partially overlaps with the activation of the ER-associated protein degradation pathway. The DNA repair protein Rad23p and its mammalian homologues have been shown to inhibit degradation of specific substrates in response to DNA damage. Particularly the recently identified inhibition of degradation by mouse Rad23 protein (mHR23) of the associated nucleotide excision repair protein XPC was shown to stimulate DNA repair.Recently, it was shown that Rad23p and the mouse homologue mHR23B also associate with Png1p, a deglycosylation enzyme. Png1p-mediated deglycosylation plays a role in ER-associated protein degradation after accumulation of malfolded proteins in the endoplasmic reticulum. Thus, if stabilization of proteins that are associated with the C-terminus of Rad23p is a general phenomenon, then Rad23 might be implicated in the stimulation of ER-associated protein degradation as well. Interestingly, the recently identified HHR23-like protein Mif1 is also thought to play a role in ER-associated protein degradation. The MIF1 gene is strongly activated in response to ER-stress. Mif1 contains a ubiquitin-like domain which is most probably involved in binding to S5a, a subunit of the 19S regulatory complex of the 26S proteasome. On the basis of its localization in the ER-membrane, it is hypothesized that Mif1 could play a role in the translocation of the 26S proteasome towards the ER-membrane, thereby enhancing ER-associated protein degradation. 相似文献