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71.
Hideo Inoue Masaki Shimizu Takako Furukawa Takashi Tamura Miwa Matsui Eiko Ohtsuka 《Nucleosides, nucleotides & nucleic acids》2013,32(6-7):1503-1505
Abstract 2′-Deoxy- and 2′-O-methyl-5′-O-terpyridyl derivatives of adenosine and cytidine were synthesized and used to construct 5′-end-modified oligonucleotides. These antisense agents complexed with Cu(II) exclusively cleaved a complementary RNA oligomer at the site opposite the terpyridine-nucleoside residue. We also found that the terpyridine·Cu(II) moiety stabilizes 2′-O-methyl RNA duplex. These suggest that after RNA hybridization, the terpyridine moiety is close to the RNA strand, presumably in an end capping manner. 相似文献
72.
Hiroyuki Hayakawa Hiromichi Tanaka Kazuhiro Haraguchi Masami Mayumi Masako Nakajima Takashi Sakamaki 《Nucleosides, nucleotides & nucleic acids》2013,32(1):121-128
Abstract Chlorination of purine nucleosides protected with tert-butyldimethylsilyl (TBDMS) group was examined by the reaction of the C-8 lithiated species, generated by LDA, with p-toluenesulfonyl chloride as an electrophile. This provides a new method for the preparation of 8-chloropurine nucleosides. 相似文献
73.
The sirtuins are members of the NAD+-dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a ΔhstD strain. Genetic interaction analysis of hstD/Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi. 相似文献
74.
Kazuhiro Shiizaki Masanobu Kawanishi Takashi Yagi 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2013,750(1-2):77-85
Benzo[a]pyrene (BaP) is metabolically activated by cytochrome P450 enzymes, and forms DNA adduct leading to mutations. Cytochrome P450 1A1 plays a central role in this activation step, and this enzyme is strongly induced by chemical agents that bind to the aryl hydrocarbon receptor (AhR), which is also known as a dioxin receptor. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent AhR ligand has not been shown to form any DNA adduct, but has a possibility to aggravate the toxicity of precarcinogenic polycyclic hydrocarbons through the induction of metabolic enzymes. We treated human hepatoma cells (HepG2) with TCDD, and subsequently exposed them to BaP to elucidate the synergistic effects on mutations. Surprisingly, mutant frequency induced by BaP at the hypoxanthine-guanine phosphribosyltransferase (HPRT) locus was decreased by pretreatment with TCDD. In correlation with decrease in the mutant frequencies, BaP–DNA adduct formation was also decreased by TCDD pretreatment. This suppressive effect of TCDD was more potent when the cells were exposed to (±)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), a reactive metabolic intermediate of BaP. Among the enzymes catalyzing BaP oxidation and conjugation, cytochrome P450 1A1, 1A2, 3A4 and UDP-glucuronosyltransferase 1A1 mRNAs were induced by the exposure to TCDD. In cytochrome P450 1A1-deficient murine cells and cytochrome P450 1A1-uninducible human cells, TCDD could not suppress BPDE–DNA adduct formation. Further experiments using “Tet-On” cytochrome P450 1A1-overexpressing cells and a recombinant cytochrome P450 1A1 enzyme demonstrated that this is the key enzyme involved in the biotransformation of BaP, that is, both production and inactivation of BPDE. We conclude that TCDD-induced cytochrome P450 catalyzes the metabolism of BPDE to as yet-unidentified products that are not apparently DNA-reactive, thereby reducing mutations in hepatoma cells. 相似文献
75.
Hiroko Tabunoki Hiromasa Ono Hiroaki Ode Kazuhiro Ishikawa Natsuki Kawana Yutaka Banno Toru Shimada Yuki Nakamura Kimiko Yamamoto Jun-ichi Satoh Hidemasa Bono 《PloS one》2013,8(7)
Plasma uric acid (UA) levels decrease following clinical progression and stage development of Parkinson’s disease (PD). However, the molecular mechanisms underlying decreases in plasma UA levels remain unclear, and the potential to apply mutagenesis to a PD model has not previously been discovered. We identified a unique mutant of the silkworm Bombyx mori (B.mori) op. Initially, we investigated the causality of the phenotypic “op” by microarray analysis using our constructed KAIKO functional annotation pipeline. Consequently, we found a novel UA synthesis-modulating pathway, from DJ-1 to xanthine oxidase, and established methods for large-scale analysis of gene expression in B. mori. We found that the mRNA levels of genes in this pathway were significantly lower in B. mori op mutants, indicating that downstream events in the signal transduction cascade might be prevented. Additionally, levels of B.mori tyrosine hydroxylase (TH) and DJ-1 mRNA were significantly lower in the brain of B. mori op mutants. UA content was significantly lower in the B. mori op mutant tissues and hemolymph. The possibility that the B. mori op mutant might be due to loss of DJ-1 function was supported by the observed vulnerability to oxidative stress. These results suggest that UA synthesis, transport, elimination and accumulation are decreased by environmental oxidative stress in the B. mori op mutant. In the case of B. mori op mutants, the relatively low availability of UA appears to be due both to the oxidation of DJ-1 and to its expenditure to mitigate the effects of environmental oxidative stress. Our findings are expected to provide information needed to elucidate the molecular mechanism of decreased plasma UA levels in the clinical stage progression of PD. 相似文献
76.
Nakarin Suwannarach Jaturong Kumla Boonsom Bussaban Kevin D. Hyde Kenji Matsui Saisamorn Lumyong 《Annals of microbiology》2013,63(4):1341-1351
The genus Muscodor comprises fungal endophytes which produce mixtures of volatile compounds (VOCs) with antimicrobial activities. In the present study, four novel species, Muscodor musae, M. oryzae, M. suthepensis and M. equiseti were isolated from Musa acuminata, Oryza rufipogon, Cinnamomum bejolghota and Equisetum debile, respectively; these are medicinal plants of northern Thailand. The new Muscodor species are distinguished based on morphological and physiological characteristics and on molecular analysis of ITS-rDNA. Volatile compound analysis showed that 2-methylpropanoic acid was the main VOCs produced by M. musae, M. suthepensis and M. equiseti. The mixed volatiles from each fungus showed in vitro antimicrobial activity. Muscodor suthepensis had the highest antifungal activity. 相似文献
77.
Hui Jiao Hiroshi Manya Shuo Wang Yanzhi Zhang Xiaoqing Li Jiangxi Xiao Yanling Yang Kazuhiro Kobayashi Tatsushi Toda Tamao Endo Xiru Wu Hui Xiong 《Molecular genetics and genomics : MGG》2013,288(7-8):297-308
Muscle-eye-brain (MEB) disease is a congenital muscular dystrophy (CMD) phenotype characterized by hypotonia at birth, brain structural abnormalities and ocular malformations. To date, few MEB cases have been reported in China where clinical recognition and genetic confirmatory testing on a research basis are recent developments. Here, we report the clinical and molecular genetics of three MEB disease patients. The patients had different degrees of muscle, eye and brain symptoms, ranging from congenital hypotonia, early-onset severe myopia and mental retardation to mild weakness, independent walking and language problems. This confirmed the expanding phenotypic spectrum of MEB disease with varying degrees of hypotonia, myopia and cognitive impairment. Brain magnetic resonance imaging showed cerebellar cysts, hypoplasia and characteristic brainstem flattening and kinking. Four candidate genes (POMGnT1, FKRP, FKTN and POMT2) were screened, and six POMGnT1 mutations (four novel) were identified, including five missense and one splice site mutation. Pathogenicity of the two novel variants in one patient was confirmed by POMGnT1 enzyme activity assay, protein expression and subcellular localization of mutant POMGnT1 in HeLa cells. Transfected cells harboring this patient’s L440R mutant POMGnT1 showed POMGnT1 mislocalization to both the Golgi apparatus and endoplasmic reticulum. We have provided clinical, histological, enzymatic and genetic evidence of POMGnT1 involvement in three unrelated MEB disease patients in China. The identification of novel POMGnT1 mutations and an expanded phenotypic spectrum contributes to an improved understanding of POMGnT1 structure–function relationships, CMD pathophysiology and genotype–phenotype correlations, while underscoring the need to consider POMGnT1 in Chinese MEB disease patients. 相似文献
78.
Kazuhiro Tajima-Pozo Ana Montes-Montero Itziar Güemes Sara González-Vives Marina Díaz-Marsá José Luis Carrasco 《Endocrinología y nutrición》2013,60(7):396-403
Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1 mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for deteting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis.Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. 相似文献
79.
Mayumi Hachinohe Midori Yamane Daiki Akazawa Kazuhiro Ohsawa Mayumi Ohno Yuzu Terashita Hiroshi Masumoto 《PloS one》2013,8(1)
The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan. 相似文献
80.
Muichi Kaito Shin-Ichi Araya Yuichiro Gondo Michiyo Fujita Naomi Minato Megumi Nakanishi Makoto Matsui 《PloS one》2013,8(8)