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21.
Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells 总被引:7,自引:0,他引:7
Koizumi S Rosa P Willars GB Challiss RA Taverna E Francolini M Bootman MD Lipp P Inoue K Roder J Jeromin A 《The Journal of biological chemistry》2002,277(33):30315-30324
Neuronal calcium sensor-1 (NCS-1) or the originally identified homologue frequenin belongs to a superfamily of EF-hand calcium binding proteins. Although NCS-1 is thought to enhance synaptic efficacy or exocytosis mainly by activating ion channel function, the detailed molecular basis for the enhancement is still a matter of debate. Here, mechanisms underlying the NCS-1-evoked enhancement of exocytosis were investigated using PC12 cells overexpressing NCS-1. NCS-1 was found to have a broad distribution in the cells being partially distributed in the cytosol and associated to vesicles and tubular-like structures. Biochemical and immunohistochemical studies indicated that NCS-1 partially colocalized with the light synaptic vesicle marker synaptophysin. When stimulated with UTP or bradykinin, agonists to phospholipase C-linked receptors, NCS-1 enhanced the agonist-mediated elementary and global Ca2+ signaling and increased the levels of downstream signals of phosphatidylinositol 4-kinase. NCS-1 enhanced the UTP-evoked exocytosis but not the depolarization-evoked Ca2+ responses or exocytosis, suggesting that the enhancement by NCS-1 should involve phospholipase C-linked receptor-mediated signals rather than the Ca2+ channels or exocytotic machinery per se. Taken together, NCS-1 enhances phosphoinositide turnover, resulting in enhancement of Ca2+ signaling and exocytosis. This is a novel regulatory mechanism of exocytosis that might involve the activation of phosphatidylinositol 4-kinase. 相似文献
22.
Inoue K Koizumi S Fuziwara S Denda S Inoue K Denda M 《Biochemical and biophysical research communications》2002,291(1):124-129
Vanilloid receptor subtype 1, VR1, is an ion channel that serves as a polymodal detector of pain-producing chemicals such as capsaicin and protons in primary afferent neurons. Here we showed that both capsaicin and acidification produced elevations in the intracellular Ca(2+) concentration ([Ca(2+)](i)) in cultured human epidermal keratinocytes. The capsaicin- and acidification-evoked increases in [Ca(2+)](i) were inhibited by capsazepine, an antagonist to VR1. VR1-like immunoreactivity was observed in the cells. These findings suggest that functional VR1-like protein is present and functions as a sensor against noxious chemical stimuli, such as capsaicin or acidification, in epidermal keratinocytes. 相似文献
23.
Horiguchi K Keef KD Ward SM 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(5):G756-G767
Electrical and mechanical activity of the circular muscle layer in the rectoanal region of the gastrointestinal tract undergoes considerable changes in the site of dominant pacemaking activity, frequency, and waveform shape. The present study was performed to determine whether changes in the structural organization of the circular layer or in the density, distribution, and ultrastructure of interstitial cells of Cajal (ICC) could account for this heterogeneity in electrical and mechanical activities. Light microscopy revealed that the structural organization of the circular muscle layer underwent dramatic morphological changes, from a tightly packed layer with poorly defined septa in the proximal rectum to one of discrete muscle bundles separated by large septae in the internal anal sphincter. Kit immunohistochemistry revealed a dense network of ICC along the submucosal and myenteric borders in the rectum, whereas in the internal anal sphincter, ICC were located along the periphery of muscle bundles within the circular layer. Changes in electrical activity within the circular muscle layer can be partially explained by changes in the structure of the muscle layer and changes in the distribution of ICC in the rectoanal region of the gastrointestinal tract. 相似文献
24.
Totani K Kubota T Kuroda T Murata T Hidari KI Suzuki T Suzuki Y Kobayashi K Ashida H Yamamoto K Usui T 《Glycobiology》2003,13(5):315-326
Highly water-soluble glycopolymers with poly(alpha-L-glutamic acid) (PGA) backbones carrying multivalent sialyl oligosaccharides units were chemoenzymatically synthesized as polymeric inhibitors of infection by human influenza viruses. p-Aminophenyl disaccharide glycosides were coupled with gamma-carboxyl groups of PGA side chains and enzymatically converted to Neu5Acalpha2-3Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-6Galbeta1-4GlcNAcbeta-, Neu5Acalpha2-3Galbeta1-3GalNAcalpha-, and Neu5Acalpha2-3Galbeta1-3GalNAcbeta- units, respectively, by alpha2,3- or alpha2,6-sialytransferases. The glycopolymers synthesized were used for neutralization of human influenza A and B virus infection as assessed by measurement of the degree of cytopathic inhibitory effect in virus-infected MDCK cells. Among the glycopolymers tested, alpha2,6-sialo-PGA with a high molecular weight (260 kDa) most significantly inhibited infection by an influenza A virus, strain A/Memphis/1/71 (H3N2), which predominantly binds to alpha2-6 Neu5Ac residue. The alpha2,6-sialo-PGA also inhibited infection by an influenza B virus, B/Lee/40. The binding preference of viruses to terminal sialic acids was affected by core determinants of the sugar chain, Galbeta1-4GlcNAcbeta- or Galbeta1-3GalNAcalpha/beta- units. Inhibition of infection by viruses was remarkably enhanced by increasing the molecular weight and sialic acid content of glycopolymers. 相似文献
25.
Xue Peng Takashi Egashira Kaoru Hanashiro Eiji Masai Seiji Nishikawa Yoshihiro Katayama Kazuhide Kimbara Masao Fukuda 《Applied and environmental microbiology》1998,64(7):2520-2527
Sphingomonas paucimobilis SYK-6 transforms 2,2′-dihydroxy-3,3′-dimethoxy-5,5′-dicarboxybiphenyl (DDVA), a lignin-related biphenyl compound, to 5-carboxyvanillic acid via 2,2′,3-trihydroxy-3′-methoxy-5,5′-dicarboxybiphenyl (OH-DDVA) as an intermediate (15). The ring fission of OH-DDVA is an essential step in the DDVA degradative pathway. A 15-kb EcoRI fragment isolated from the cosmid library complemented the growth deficiency of a mutant on OH-DDVA. Subcloning and deletion analysis showed that a 1.4-kb DNA fragment included the gene responsible for the ring fission of OH-DDVA. An open reading frame encoding 334 amino acids was identified and designated ligZ. The deduced amino acid sequence of LigZ had 18 to 21% identity with the class III extradiol dioxygenase family, including the β subunit (LigB) of protocatechuate 4,5-dioxygenase of SYK-6 (Y. Noda, S. Nishikawa, K.-I. Shiozuka, H. Kadokura, H. Nakajima, K. Yano, Y. Katayama, N. Morohoshi, T. Haraguchi, and M. Yamasaki, J. Bacteriol. 172:2704–2709, 1990), catechol 2,3-dioxygenase I (MpcI) of Alcaligenes eutrophus JMP222 (M. Kabisch and P. Fortnagel, Nucleic Acids Res. 18:3405–3406, 1990), the catalytic subunit of the meta-cleavage enzyme (CarBb) for 2′-aminobiphenyl-2,3-diol from Pseudomonas sp. strain CA10 (S. I. Sato, N. Ouchiyama, T. Kimura, H. Nojiri, H. Yamane, and T. Omori, J. Bacteriol. 179:4841–4849, 1997), and 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB) of Escherichia coli (E. L. Spence, M. Kawamukai, J. Sanvoisin, H. Braven, and T. D. H. Bugg, J. Bacteriol. 178:5249–5256, 1996). The ring fission product formed from OH-DDVA by LigZ developed a yellow color with an absorption maximum at 455 nm, suggesting meta cleavage. Thus, LigZ was concluded to be a ring cleavage extradiol dioxygenase. LigZ activity was detected only for OH-DDVA and 2,2′,3,3′-tetrahydroxy-5,5′-dicarboxybiphenyl and was dependent on the ferrous ion.Lignin is the most common aromatic compound in the biosphere, and the degradation of lignin is a significant step in the global carbon cycle. Lignin is composed of various intermolecular linkages between phenylpropanes and guaiacyl, syringyl, p-hydroxyphenyl, and biphenyl nuclei (5, 34). Lignin breakdown therefore involves multiple biochemical reactions involving the cleavage of intermonomeric linkages, demethylations, hydroxylations, side-chain modifications, and aromatic ring fission (10, 11, 19, 40).Soil bacteria are known to display ample metabolic versatility toward aromatic substrates. Sphingomonas paucimobilis SYK-6 (formerly Pseudomonas paucimobilis SYK-6) has been isolated with 2,2′-dihydroxy-3,3′-dimethoxy-5,5′-dicarboxybiphenyl (DDVA) as a sole carbon and energy source. This strain can also grow on syringate, 3-O-methylgallic acid (3OMGA), vanillate, and other dimeric lignin compounds, including β-aryl ether, diarylpropane (β-1), and phenylcoumaran (15). Analysis of the metabolic pathway has indicated that the dimeric lignin compounds are degraded to protocatechuate or 3OMGA (15) and that these compounds are cleaved by protocatechuate 4,5-dioxygenase encoded by ligAB (30). Among the dimeric lignin compounds, the degradation of β-aryl ether and the biphenyl structure is the most important, because β-aryl ether is most abundant in lignin (50%) and the biphenyl structure is so stable that its decomposition should be rate limiting in lignin degradation. We have already characterized the β-etherase and Cα-dehydrogenase genes (23–26) (ligFE and ligD, respectively) involved in the degradation of β-aryl ether. In this study, we focused on the genes responsible for the degradation of DDVA in SYK-6.In the proposed DDVA metabolic pathway of S. paucimobilis SYK-6 illustrated in Fig. Fig.1A,1A, DDVA is first demethylated to produce the diol compound 2,2′,3-trihydroxy-3′-methoxy-5,5′-dicarboxybiphenyl (OH-DDVA). OH-DDVA is then degraded to 5-carboxyvanillic acid (5-CVA), and this compound is converted to 3OMGA (15). The resulting product is cleaved by protocatechuate 4,5-dioxygenase. A ring cleavage enzyme for OH-DDVA has been thought to be involved in this pathway because the production of 5-CVA from OH-DDVA resembles the formation of benzoic acid from biphenyl by 2,3-dihydroxybiphenyl through the sequential action of a meta cleavage enzyme and a meta-cleavage compound hydrolase (Fig. (Fig.1B)1B) (1, 9, 13, 18, 21, 28). Open in a separate windowFIG. 1(A) Proposed metabolic pathway for DDVA by S. paucimobilis SYK-6. (B) Pathway for the conversion of 2,3-dihydroxybiphenyl (2,3-DHBP) to benzoate by the polychlorinated biphenyl-degrading bacteria. The proposed DDVA metabolic pathway follows the previous one (15). Enzymes: LigZ, OH-DDVA oxygenase; LigAB, protocatechuate 4,5-dioxygenase; BphC, 2,3-dihydroxybiphenyl 1,2-dioxygenase; BphD, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid hydrolase. TCA, tricarboxylic acid.In this study, we isolated the ligZ gene encoding a ring cleavage enzyme for OH-DDVA. The nucleotide sequence of the gene was determined, and the ligZ gene product was characterized. 相似文献
26.
Manabu Yamada Mitsuji Yamashita Takuya Suyama Junko Yamashita Kazuhide Asai Taishi Niimi Nobuhisa Ozaki Michio Fujie Kasthuraiah Maddali Satoki Nakamura Kazunori Ohnishi 《Bioorganic & medicinal chemistry letters》2010,20(19):5943-5946
4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect. 相似文献
27.
Identification and Characterization of a Constitutively Active STAT5 Mutant That Promotes Cell Proliferation 总被引:24,自引:2,他引:24
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28.
Toshio Watanabe Toshihisa Takeuchi Osamu Handa Yasuhisa Sakata Tetsuya Tanigawa Masatsugu Shiba Yuji Naito Kazuhide Higuchi Kazuma Fujimoto Toshikazu Yoshikawa Tetsuo Arakawa 《PloS one》2015,10(4)
Background
Low-dose aspirin (LDA) frequently causes small bowel injury. While some drugs have been reported to be effective in treating LDA-induced small intestinal damage, most studies did not exclude patients with mild damage thought to be clinically insignificant.Aim
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy of a high dose of rebamipide, a gastroprotective drug, for LDA-induced moderate-to-severe enteropathy.Methods
We enrolled patients who received 100 mg of enteric-coated aspirin daily for more than 3 months and were found to have more than 3 mucosal breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy. Eligible patients were assigned to receive either rebamipide 300 mg (triple dose) 3 times daily or placebo for 8 weeks in a 2:1 ratio. Capsule endoscopy was then repeated. The primary endpoint was the change in the number of mucosal breaks from baseline to 8 weeks. Secondary endpoints included the complete healing of mucosal breaks at 8 weeks and the change in Lewis score (an endoscopic score assessing damage severity) from baseline to 8 weeks.Results
The study was completed by 38 patients (rebamipide group: n = 25, placebo group: n = 13). After 8 weeks of treatment, rebamipide, but not placebo, significantly decreased the number of mucosal breaks (p = 0.046). While the difference was not significant (p = 0.13), the rate of complete mucosal break healing in the rebamipide group (32%, 8 of 25) tended to be higher than that in the placebo group (7.7%, 1 of 13). Rebamipide treatment significantly improved intestinal damage severity as assessed by the Lewis score (p = 0.02), whereas placebo did not. The triple dose of rebamipide was well tolerated.Conclusions
High-dose rebamipide is effective for the treatment of LDA-induced moderate-to-severe enteropathy.Trial Registration
UMIN Clinical Trials Registry UMIN000003463 相似文献29.
The ethoxy chains of short ethoxy chain nonylphenol (NPEOav2.0, containing average 2.0 ethoxy units) were dehydrogenated by cell-free extracts from Ensifer sp. strain AS08 grown on a basal medium supplemented with NPEOav2.0. The reaction was coupled with the reduction in 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and phenazine
methosulfate. The enzyme (NPEOav2.0 dehydrogenase; NPEO-DH) was purified to homogeneity with a yield of 20% and a 56-fold increase in specific activity. The
molecular mass of the native enzyme was 120 kDa, consisting of two identical monomer units (60 kDa). The gene encoding NPEO-DH
was cloned, which consisted of 1,659 bp, corresponding to a protein of 553 amino acid residues. The deduced amino acid sequence
agreed with the N-terminal amino acid sequence of the purified NPEO-DH. The presence of a flavin adenine dinucleotide (FAD)-binding
motif and glucose–methanol–choline (GMC) oxidoreductase signature motifs strongly suggested that the enzyme belongs to the
GMC oxidoreductase family. The protein exhibited homology (40–45% identity) with several polyethylene glycol dehydrogenases
(PEG-DHs) of this family, but the identity was lower than those (approximately 58%) among known PEG-DHs. The substrate-binding
domain was more hydrophobic compared with those of glucose oxidase and PEG-DHs. The recombinant protein had the same molecular
mass as the purified NPEO-DH and dehydrogenated PEG400-2000, NPEOav2.0 and its components, and NPEOav10, but only slight or no activity was found using diethylene glycol, triethylene glycol, and
PEG200.
English edition: The paper was edited by a native speaker through American Journal Experts (). 相似文献
30.
Hu X Fukutani A Liu X Kimbara K Kawai F 《Applied microbiology and biotechnology》2007,73(6):1407-1413
Two bacterial consortia growing on a random copolymer of ethylene glycol and propylene glycol units were obtained by enrichment
cultures from various microbial samples. Six major strains included in both consortia were purified and identified as Sphingomonads,
Pseudomonas sp. and Stenotrophomonas maltophilia. Three of them (Sphingobium sp. strain EK-1, Sphingopyxis macrogoltabida strain EY-1, and Pseudomonas sp. strain PE-2) utilized both PEG and polypropylene glycol (PPG) as a sole carbon source. Four PEG-utilizing bacteria had
PEG dehydrogenase (PEG-DH) activity, which was induced by PEG. PCR products from DNA of these bacteria generated with primers
designed from a PEG-DH gene (AB196775 for S. macrogoltabida strain 103) indicated the presence of a sequence that is the homologous to the PEG-DH gene (99% identity). On the other hand,
five PPG-utilizing bacteria had PPG dehydrogenase (PPG-DH) activity, but the activity was constitutive. PCR of a PPG-DH gene
was performed using primers designed from a polyvinyl alcohol dehydrogenase (PVA-DH) gene (AB190288 for Sphingomonas sp. strain 113P3) because a PPG-DH gene has not been cloned yet, but both PPG-DH and PVA-DH were active toward PPG and PVA
(Mamoto et al. 2006). PCR products of the five strains did not have similarity to each other or to oxidoreductases including PVA-DH.
The paper was edited by a native speaker through American Journal Experts (http://www.journalexperts.com). 相似文献