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51.
52.
Wild‐type and specific mutant androgen receptor mediates transcription via 17β‐estradiol in sex hormone‐sensitive cancer cells 下载免费PDF全文
Takao Susa Reina Ikaga Takashi Kajitani Masayoshi Iizuka Hiroko Okinaga Mimi Tamamori‐Adachi Tomoki Okazaki 《Journal of cellular physiology》2015,230(7):1594-1606
We previously encountered regulatory processes wherein dihydrotestosterone (DHT) exerted its inhibitory effect on parathyroid hormone‐related protein (PTHrP) gene repression through the estrogen receptor (ER)α, but not the androgen receptor (AR), in breast cancer MCF‐7 cells. Here, we investigated whether such aberrant ligand‐nuclear receptor (NR) interaction is present in prostate cancer LNCaP cells. First, we confirmed that LNCaP cells expressed large amounts of AR at negligible levels of ERα/β or progesterone receptor. Both suppression of PTHrP and activation of prostate‐specific antigen genes were observed after independent administration of 17β‐estradiol (E2), DHT, or R5020. Consistent with the notion that the LNCaP AR lost its ligand specificity due to a mutation (Thr‐Ala877), experiments with siRNA targeting the respective NR revealed that the AR monopolized the role of the mediator of shared hormone‐dependent regulation, which was invariably associated with nuclear translocation of this mutant AR. Microarray analysis of gene regulation by DHT, E2, or R5020 disclosed that more than half of the genes downstream of the AR (Thr‐Ala877) overlapped in the LNCaP cells. Of particular interest, we realized that the AR (wild‐type [wt]) and AR (Thr‐Ala877) were equally responsible for the E2‐AR interactions. Fluorescence microscopy experiments demonstrated that both EGFP‐AR (wt) and EGFP‐AR (Thr‐Ala877) were exclusively localized within the nucleus after E2 or DHT treatment. Furthermore, reporter assays revealed that some other cancer cells exhibited aberrant E2‐AR (wt) signaling similar to that in the LNCaP cells. We herein postulate the presence of entangled interactions between wt AR and E2 in certain hormone‐sensitive cancer cells. J. Cell. Physiol. 230: 1594–1606, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 相似文献
53.
Tatsuhisa Tsuboi Reina Yamazaki Risa Nobuta Ken Ikeuchi Shiho Makino Ayumi Ohtaki Yutaka Suzuki Tohru Yoshihisa Christopher Trotta Toshifumi Inada 《The Journal of biological chemistry》2015,290(26):16021-16030
The tRNA splicing endonuclease (Sen) complex is located on the mitochondrial outer membrane and splices precursor tRNAs in Saccharomyces cerevisiae. Here, we demonstrate that the Sen complex cleaves the mitochondria-localized mRNA encoding Cbp1 (cytochrome b mRNA processing 1). Endonucleolytic cleavage of this mRNA required two cis-elements: the mitochondrial targeting signal and the stem-loop 652–726-nt region. Mitochondrial localization of the Sen complex was required for cleavage of the CBP1 mRNA, and the Sen complex cleaved this mRNA directly in vitro. We propose that the Sen complex cleaves the CBP1 mRNA, which is co-translationally localized to mitochondria via its mitochondrial targeting signal. 相似文献
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Reina Wada Masanaru Ozaki Takashi Kumon Hiromichi Ohta 《Biocatalysis and Biotransformation》2015,33(3):188-190
A GGG(A)X-type esterase (Est0071) from an archaeon catalyzes asymmetric hydrolysis of prochiral bulky malonic diesters in good enantioselectivity. The selectivity of Est0071 was for the opposite enantiomer to that previously shown for pig liver esterase, and the resulting enantiomeric excess of the products was higher. Est0071 could also catalyze the hydrolysis of various acetates of secondary alcohols, and showed moderate enantioselectivity in these reactions. 相似文献
57.
Reina M Ruiz-Mesia W Ruiz-Mesia L Martínez-Díaz R González-Coloma A 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(5-6):225-234
Five oxindole alkaloids, three plumerane-type alkaloids, subtype haplophitine, and one aspidospermatane-type alkaloid, subtype tubotaiwine, were isolated from the medicinal plants Aspidosperma rigidum and A. schultesii. One compound was identified as the transoid conformer of 18-oxo-O-methylaspidoalbine which was not previously described. The antiparasitic activity of all compounds against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity against mammalian cells were also determined. 相似文献
58.
Shimegi T Takusagawa Y Ohtsuki T Noda S Kurisu G Kusunoki M Ui S 《Protein and peptide letters》2011,18(8):825-830
The development of a stable L-BDH chimera was attempted by exchanging whole domains between two native structural analogs, L-BDH and meso-BDH, because the S-configuration specificity of L-BDH is valuable from the standpoint of its application but its activity is unstable, whereas meso-BDH is stable. The domain chimeras obtained indicated that the leaf-like structures constituting three domains were likely to be mainly associated with chiral recognition, and the fourth domain, the basic domain, is likely to be mainly associated with enzyme stability. A combination of the leaf domains of L-BDH and the basic domain of meso-BDH attained a sufficient level of practical use as an artificial L-BDH chimera, because the resulting enzyme had both stability and S-configuration specificity. However, the levels of stability and specificity were slightly lower than those of the respective enzymes from which they were derived. 相似文献
59.
Mazoir N Benharref A Bailén M Reina M González-Coloma A Martínez-Díaz RA 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(7-8):360-366
The in vitro activity on Leishmania infantum promastigotes and Trypanosoma cruzi epimastigotes of 25 semisynthetic terpenoid derivatives has been evaluated. These compounds were obtained through chemical modifications of the major components of Euphorbia resinifera (alpha-euphol and alpha-euphorbol) and Euphorbia officinarum (obtusifoliol and 31-norlanosterol). Leishmaniasis and Chagas' disease are major worldwide health problems. The drugs of choice for their treatment are still problematic in both cases, and therefore there is an urgent need to discover new drugs with high activity and low side effects. Natural products have become a key source of new drugs in the last years. The genus Euphorbia has been the subject of abundant phytochemical and pharmacological research because of its potential medical applications, but the antiparasitic effects of derivatives from plants of this genus are still unknown. Our results showed that 76% and 64% of the test compounds had antiparasitic effects on L. infantum and T cruzi, respectively. The different activities on both parasites, especially their moderate effects on mammalian cells, indicate an interesting selective toxicity. 相似文献
60.
Fox BM Natero R Richard K Connors R Roveto PM Beckmann H Haller K Golde J Xiao SH Kayser F 《Bioorganic & medicinal chemistry letters》2011,21(8):2460-2467
We discovered novel pyrrolidine MCHR1 antagonist 1 possessing moderate potency. Profiling of pyrrolidine 1 demonstrated that it was an inhibitor of the hERG channel. Investigation of the structure-activity relationship of this class of pyrrolidines allowed us to optimize the MCHR1 potency and decrease the hERG inhibition. Increasing the acidity of the amide proton by converting the benzamide in lead 1 to an anilide provided single digit nanomolar MCHR1 antagonists while replacing the dimethoxyphenyl ring of 1 with alkyl groups possessing increased polarity dramatically reduced the hERG inhibition. 相似文献