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61.
Quinones are widely distributed in the environment, both as natural products and as pollutants. This paper reports that one
of the simplest quinones, 2-methyl-1,4-naphthoquinone (menadione), effectively inhibited apoptosis in the presence of UVA.
Menadione suppressed the apoptosis induced by serum depletion and cell detachment. This effect was significantly enhanced
by UVA irradiation. An antioxidant, N-acetylcysteine, completely inhibited the antiapoptotic effects of both menadione itself and menadione plus UVA, and peroxidation
of the cells after treatment was observed using a probe to detect the intracellular production of peroxides. By contrast,
2-hydroxy-1,4-naphtoquinone (lawsone) showed no antiapoptotic effect in the presence or absence of UVA. Lawsone is reported
not to undergo the redox process that produces reactive oxygen species. These results indicated that intracellular peroxidation
contributed to the antiapoptotic effects of both menadione itself and menadione plus UVA. Dysregulation of the apoptotic process
is critical to carcinogenesis. The photosensitization of quinone compounds as it relates to the inhibition of apoptosis should
be examined in the future. 相似文献
62.
Masashi Kawasaki Yuka Asano Kanako Katayama Akihisa Inoue Chiho Hiraoka Hiroko Kakuda Akira Tanaka Michimasa Goto Naoki Toyooka Tadashi Kometani 《Journal of Molecular Catalysis .B, Enzymatic》2008,54(3-4):93-102
2-Substituted 4-chromanones were synthesized in their optically active forms. The chiral intermediates were obtained via lipase-catalyzed enantioselective reactions. Lipase and esterase were also used for the hydrolysis of ester moieties of the precursors of the target compounds under mild conditions. 相似文献
63.
Matsumoto K Tomikawa C Toyooka T Ochi A Takano Y Takayanagi N Abe M Endo Y Hori H 《Journal of biotechnology》2008,133(4):453-460
Cell-free translation systems are a powerful tool for the production of many kinds of proteins. However the production of proteins made up of hetero subunits is a major problem. In this study, we selected yeast tRNA (m(7)G46) methyltransferase (Trm8-Trm82 heterodimer) as a model protein. The enzyme catalyzes a methyl-transfer from S-adenosyl-l-methionine to the N(7) atom of guanine at position 46 in tRNA. When Trm8 or Trm82 mRNA were used for cell-free translation, Trm8 and Trm82 proteins could be synthesized. Upon mixing the synthesized Trm8 and Trm82 proteins, no active Trm8-Trm82 heterodimer was produced. Active Trm8-Trm82 heterodimer was only synthesized under conditions, in which both Trm8 and Trm82 mRNAs were co-translated. These results strongly suggest that the association of the Trm8 and Trm82 subunits is translationally controlled in living cells. Kinetic parameters of purified Trm8-Trm82 heterodimer were measured and these showed that the protein has comparable activity to other tRNA methyltransferases. The production of the m(7)G base at position 46 in tRNA was confirmed by two-dimensional thin layer chromatography and aniline cleavage of the methylated tRNA. 相似文献
64.
Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development 总被引:25,自引:0,他引:25
Toyooka Y Tsunekawa N Takahashi Y Matsui Y Satoh M Noce T 《Mechanisms of development》2000,93(1-2):139-149
To demonstrate the cellular and subcellular localization of mouse vasa homologue protein during germ cell development, specific antibody was raised against the full-length MVH protein. The immunohistochemical analyses demonstrated that MVH protein was exclusively expressed in primordial germ cells just after their colonization of embryonic gonads and in germ cells undergoing gametogenic processes until the post-meiotic stage in both males and females. The co-culture of EG cells with gonadal somatic cells indicated inductive MVH expression caused by an intercellular interaction with gonadal somatic cells. In adult testis, MVH protein was localized in the cytoplasm of spermatogenic cells, including chromatoid bodies in spermatids, known to be a perinuclear nuage structure which includes polar granules that contain VASA protein in Drosophila. 相似文献
65.
Sexual differentiation of the guinea pig brain is androgen dependent. To understand the cellular mechanisms of androgen action, we studied the ontogeny of cytosolic (ARc) and nuclear (ARn) androgen receptors in the brains and anterior pituitaries of fetal, neonatal, and adult guinea pigs. Using cytosol from the hypothalamus-preoptic area-amygdala-septum of 60- to 65-day fetuses and nuclear preparations from 6-day-old neonates treated with testosterone propionate, validation studies revealed an AR with an apparent Kd of 1.9 +/- 1.1 (mean +/- SEM, n = 3) x 10(-10) M (ARc) and 3.4 +/- 3.2 (n = 3) x 10(-10) M (ARn). The cytosolic receptors were highly specific for androgens. After assay validation, AR content was determined from specific brain regions of fetuses obtained on Days 30, 40, 50, and 59 of gestation and on Days 6 and 120 postpartum. ARc differed significantly (p less than 0.05) between brain regions and times of gestation, but no sex differences were apparent. In contrast, ARn showed little difference between tissues or with gestational age, but there were significant differences between males and females, especially in late gestation and early postnatal life, with males having greater ARn binding (p less than 0.05). These data demonstrate the presence of ARc and ARn in the fetal brain and pituitary gland during the critical period of sexual differentiation (Days 30-37 of gestation), thus establishing the identity of cellular structures involved in androgen action. 相似文献
66.
Toyooka N Kobayashi S Zhou D Tsuneki H Wada T Sakai H Nemoto H Sasaoka T Garraffo HM Spande TF Daly JW 《Bioorganic & medicinal chemistry letters》2007,17(21):5872-5875
We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of alpha7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked alpha7 and alpha4beta2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of alpha7 and alpha4beta2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce alpha7-potency without affecting alpha4beta2-potency. 相似文献
67.
68.
T. Minamikawa K. Toyooka T. Okamoto I. Hara-Nishimura M. Nishimura 《Protoplasma》2001,218(3-4):144-153
Summary The possible involvement of vacuolar cysteine proteinases in degradation of ribulose-bisphosphate carboxylase (Rubisco) in senescing French bean leaves was studied by ultrastructural and immunocytochemical analyses with antibodies raised against the large subunit (LSU) of Rubisco and SH-EP, a cysteine proteinase fromVigna mungo that is immunologically identical to one of the major proteinases of French bean plants. Primary leaves of 10-day-old plants were detached and placed at 25 °C in darkness for 0, 4, and 8 days to allow their senescence to proceed. The leaves at each senescence stage were subjected to the conventional electron microscopic and immunocytochemical studies. The results indicated that the chloroplasts of senescing French bean leaves were separated from the cytoplasm of the cell periphery and taken into the central vacuole and that the Rubisco LSU in the chloroplasts was degraded by vacuolar enzymes such as an SH-EP-related cysteine proteinase that developed in senescing leaves. The present results together with the results of previous biochemical studies using vacuolar lysates support the view that Rubisco is degraded through the association of chloroplasts with the central vacuole during the senescence of leaves that were detached and placed in darkness. 相似文献
69.
Huy Du Nguyen Takuya Okada Shun Kitamura Sakura Yamaoka Yamato Horaguchi Yoshihito Kasanami Fumiko Sekiguchi Maho Tsubota Shigeru Yoshida Hiroyuki Nishikawa Atsufumi Kawabata Naoki Toyooka 《Bioorganic & medicinal chemistry》2018,26(15):4410-4427
Since 6-prenylnaringenin (6-PNG) was recently identified as a novel T-type calcium channel blocker with the IC50 value around 1?µM, a series of flavanone derivatives were designed, synthesized and subsequently evaluated for T-channel-blocking activity in HEK293 cells transfected with Cav3.2?T-type channels using a patch-clamp technique. As a result, several new flavanones blocked Cav3.2-dependent T-currents more potently than 6-PNG. In the synthesized compounds, 6-(3-ethylpent-2-enyl)-5,7-dihydroxy-2-(2-hydroxyphenyl)chroman-4-one 8j, 6-(3-ethylpent-2-enyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 11b, 6-(2-cyclopentylideneethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 11d, and 6-(2-Cyclopentylethyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one 12c were more potent blocker than 6-PNG with the IC50 value of 0.39, 0.26, 0.46, and 0.50?µM, respectively. Among the above four derivatives, the compound 8j provided the best result in the in vivo experiments; i.e. systemic administration of 8j at the minimum dose completely restored neuropathic pain induced by partial sciatic nerve ligation in mice. 相似文献
70.
Shota Miyawaki Yuki Hirokami Kyoko Kinami Masako Hoshino Daisuke Minehira Daiki Miyamoto Robert J. Nash George W.J. Fleet Isao Adachi Naoki Toyooka Atsushi Kato 《Bioorganic & medicinal chemistry》2017,25(1):107-115
This study shows that the cyclization of l-DMDP thioureas to bicyclic l-DMDP isothioureas improved α-l-rhamnosidase inhibition which was further enhanced by increasing the length of the alkyl chain. The addition of a long alkyl chain, such as decyl or dodecyl, to the nitrogen led to the production of highly potent inhibitors of α-l-rhamnosidase; it also caused broad inhibition spectrum against β-glucosidase and β-galactosidase. In contrast, the corresponding N-benzyl-l-DMDP cyclic isothioureas display selective inhibition of α-l-rhamnosidase; 3′,4′-dichlorobenzyl-l-DMDP cyclic isothiourea (3r) was found to display the most potent and selective inhibition of α-l-rhamnosidase, with IC50 value of 0.22 μM, about 46-fold better than the positive control 5-epi-deoxyrhamnojirimycin (5-epi-DRJ; IC50 = 10 μM) and occupied the active-site of this enzyme (Ki = 0.11 μM). Bicyclic isothioureas of ido-l-DMDP did not inhibit α-l-rhamnosidase. These new mimics of l-rhamnose may affect other enzymes associated with the biochemistry of rhamnose including enzymes involved in progression of tuberculosis. 相似文献