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91.
Yoshiaki Suzuki Hisao Yamamura Susumu Ohya Yuji Imaizumi 《The Journal of biological chemistry》2013,288(51):36750-36761
L-type voltage-dependent Ca2+ channels (LVDCC) and large conductance Ca2+-activated K+ channels (BKCa) are the major factors defining membrane excitability in vascular smooth muscle cells (VSMCs). The Ca2+ release from sarcoplasmic reticulum through ryanodine receptor significantly contributes to BKCa activation in VSMCs. In this study direct coupling between LVDCC (Cav1.2) and BKCa and the role of caveoline-1 on their interaction in mouse mesenteric artery SMCs were examined. The direct activation of BKCa by Ca2+ influx through coupling LVDCC was demonstrated by patch clamp recordings in freshly isolated VSMCs. Using total internal reflection fluorescence microscopy, it was found that a large part of yellow fluorescent protein-tagged BKCa co-localized with the cyan fluorescent protein-tagged Cav1.2 expressed in the plasma membrane of primary cultured mouse VSMCs and that the two molecules often exhibited FRET. It is notable that each BKα subunit of a tetramer in BKCa can directly interact with Cav1.2 and promotes Cav1.2 cluster in the molecular complex. Furthermore, caveolin-1 deficiency in knock-out (KO) mice significantly reduced not only the direct coupling between BKCa and Cav1.2 but also the functional coupling between BKCa and ryanodine receptor in VSMCs. The measurement of single cell shortening by 40 mm K+ revealed enhanced contractility in VSMCs from KO mice than wild type. Taken together, caveolin-1 facilitates the accumulation/clustering of BKCa-LVDCC complex in caveolae, which effectively regulates spatiotemporal Ca2+ dynamics including the negative feedback, to control the arterial excitability and contractility. 相似文献
92.
Yoshimasa Ishizaki Chigusa Hayashi Kunio Inoue Masayuki Igarashi Yoshiaki Takahashi Venugopal Pujari Dean C. Crick Patrick J. Brennan Akio Nomoto 《The Journal of biological chemistry》2013,288(42):30309-30319
Because tuberculosis is one of the most prevalent and serious infections, countermeasures against it are urgently required. We isolated the antitubercular agents caprazamycins from the culture of an actinomycete strain and created CPZEN-45 as the most promising derivative of the caprazamycins. Herein, we describe the mode of action of CPZEN-45 first against Bacillus subtilis. Unlike the caprazamycins, CPZEN-45 strongly inhibited incorporation of radiolabeled glycerol into growing cultures and showed antibacterial activity against caprazamycin-resistant strains, including a strain overexpressing translocase-I (MraY, involved in the biosynthesis of peptidoglycan), the target of the caprazamycins. By contrast, CPZEN-45 was not effective against a strain overexpressing undecaprenyl-phosphate–GlcNAc-1-phosphate transferase (TagO, involved in the biosynthesis of teichoic acid), and a mutation was found in the tagO gene of the spontaneous CPZEN-45-resistant strain. This suggested that the primary target of CPZEN-45 in B. subtilis is TagO, which is a different target from that of the parent caprazamycins. This suggestion was confirmed by evaluation of the activities of these enzymes. Finally, we showed that CPZEN-45 was effective against WecA (Rv1302, also called Rfe) of Mycobacterium tuberculosis, the ortholog of TagO and involved in the biosynthesis of the mycolylarabinogalactan of the cell wall of M. tuberculosis. The outlook for WecA as a promising target for the development of antituberculous drugs as a countermeasure of drug resistant tuberculosis is discussed. 相似文献
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95.
Mitsutaka Ogawa Naosuke Nakamura Yoshiaki Nakayama Akira Kurosaka Hiroshi Manya Motoi Kanagawa Tamao Endo Koichi Furukawa Tetsuya Okajima 《Biochemical and biophysical research communications》2013
Hypoglycosylation is a common characteristic of dystroglycanopathy, which is a group of congenital muscular dystrophies. More than ten genes have been implicated in α-dystroglycanopathies that are associated with the defect in the O-mannosylation pathway. One such gene is GTDC2, which was recently reported to encode O-mannose β-1,4-N-acetylglucosaminyltransferase. Here we show that GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes on the O-mannosylated α-dystroglycan (α-DG). Using the antibody, we show that mutations of GTDC2 identified in Walker–Warburg syndrome and alanine-substitution of conserved residues between GTDC2 and EGF domain O-GlcNAc transferase resulted in decreased glycosylation. Moreover, GTDC2-modified GlcNAc epitopes are localized in the endoplasmic reticulum (ER). These data suggested that GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of O-mannosylated α-DG in the ER. CTD110.6 antibody may be useful to detect a specific form of GlcNAcylated O-mannose and to analyze defective O-glycosylation in α-dystroglycanopathies. 相似文献
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97.
Yoshiaki Kitamura Yuki Masegi Shunsuke Ogawa Remi Nakashima Yukihiro Akao Yoshihito Ueno Yukio Kitade 《Bioorganic & medicinal chemistry》2013,21(15):4494-4501
We have developed chemically modified siRNAs and miRNAs bearing urea/thiourea-bridged aromatic compounds at their 3′-end for RNAi therapy. Chemically modified RNAs possessing urea/thiourea-bridged aromatic compounds instead of naturally occurring dinucleotides at the 3′-overhang region were easily prepared in good yields and were more resistant to nucleolytic hydrolysis than unmodified RNA. siRNAs containing urea or thiourea derivatives showed the desired knockdown effect. Furthermore, modified miR-143 duplexes carrying the urea/thiourea compounds in the 3′-end of each strand were able to inhibit the growth of human bladder cancer T24 cells. 相似文献
98.
Humio Kurasawa Yoshiaki Kanauti Koji Takei Shiroshi Ogawa Tetsutaro Okabe Toshiro Hayakawa 《Bioscience, biotechnology, and biochemistry》2013,77(10):1809-1813
A screening was designed to isolate microorganisms having poly(γ-glutamic acid) (PGA) endohydrolase activity. Of the strains screened, TM-4222, from a soil sample, showed the highest viscosity decrement ability on PGA. It was identified to be a Myrothecium sp. The fungal production of the enzyme was slightly promoted with yeast extract and greatly promoted with· both yeast extract and PGA. The fungus was evaluated to produce PGA hydrolase of an endo-type specificity by analyzing of the reaction products. 相似文献
99.
Humio Kurasawa Yoshiaki Kanauchi Tadakatsu Wakayama Toshiro Hayakawa Ikuo Igaue 《Bioscience, biotechnology, and biochemistry》2013,77(12):2913-2916
Varoius piericidin analogues (PS-I, -II and -III in Fig. 2) were synthesized from three 4-acetoxy-6-formylpyridines by Wittig reaction to determine the structure-activity relationships. New type inhibitors, 5-alkenyl-2, 3-dimethoxy-4-hydroxy-6-methylpyridines (PS-IV) were synthesized by intramolecular cyclization. 相似文献
100.
In the course of investigation of alicyclic hydrocarbon-utilizing microorganisms, five strains of ethylcyclohexane-utilizing bacteria were isolated from soil samples.Among those bacteria, the strain S6B1 that was identified as Alcaligenes faecalis, showed the best growth in shaking culture.The strain S6B1 was found to produce 4-ethylcyclohexanol from ethylcyclohexane.This substance separated from culture broth was purified and identified to be trans-4-ethylcyclohexanol by the use of NMR. 相似文献