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921.
Suzuki T Choi JH Kawaguchi T Yamashita K Morita A Hirai H Nagai K Hirose T Omura S Sunazuka T Kawagishi H 《Bioorganic & medicinal chemistry letters》2012,22(13):4246-4248
Makomotindoline (1) was isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta. The structure was determined by the interpretation of spectroscopic data and synthesis. Makomotindoline (1), its l-Glc isomer (2) and its aglycon (3) were synthesized and their effects on rat glioma cells showed adverse effects on the cell growth. 相似文献
922.
Itoh Y Ishikawa M Kitaguchi R Okuhira K Naito M Hashimoto Y 《Bioorganic & medicinal chemistry letters》2012,22(13):4453-4457
Protein knockdown can be achieved by the use of a small molecule that possesses affinity for both the target protein and ubiquitin ligase. We have designed such a degradation-inducing molecule targeting cIAP1 and CRABP-II, which are involved in proliferation of several cancer cell lines and in neuroblastoma growth, respectively. As a CRABP-II-recognizing moiety, all-trans retinoic acid (ATRA, 3), a physiological ligand of CRABP, was chosen. As a cIAP1-recognizing moiety, MV1 (5), which is a cIAP1/cIAP2/XIAP pan-ligand, was chosen. Although cIAP1 itself possesses ubiquitin ligase activity, we expected that its decomposition would be efficiently mediated by related molecules, including cIAP2 and XIAP, which also possess ubiquitin ligase activity. The designed degradation inducer 6, in which ATRA (3) and MV1 (5) moieties are connected via a linker, was synthesized and confirmed to induce efficient degradation of both cIAP1 and CRABP-II. It showed potently inhibited the proliferation of IMR32 cells. 相似文献
923.
Human heregulins are neuregulin-1 type I polypeptides that act as ligands of the ErbB family of receptor tyrosine kinases. These peptides play an essential role in the development of the cardiovascular system, including angiogenesis and compensation of cardiac function. Both heregulins and ErbB receptors are expressed at high levels in various types of vascular cells. The results of cell culture, animal, and clinical experiments have shown heregulin-β(1) to be a promising drug candidate for prevention of atherosclerosis. Various mechanisms have been suggested to be involved in this process, such as suppression of macrophage foam cell formation and vascular smooth muscle cell proliferation. Heregulin-β(1) retards pro-inflammatory responses by attenuating the expression of interleukin-1β, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, matrix metalloproteinase-9, and cyclooxygenase-2 in monocytes. The peptide also has anti-oxidant and anti-apoptotic properties, and activates endothelial nitric oxide synthase in cardiomyocytes. Chronic infusion of heregulin-β(1) into apolipoprotein E-knockout mice suppresses the development of atherosclerotic lesions. In rat balloon injury models, heregulin-β(1) injection attenuates neointimal formation in the carotid artery. Clinical studies have shown that markedly reduced levels of heregulin-β(1) in the arterial wall and blood are closely associated with the progression of human coronary atherosclerotic lesions in patients with coronary artery disease. Therefore, these findings provide insight into the potential use of heregulin-β(1) as an extended therapeutic window for combating atherosclerosis and restenosis after coronary angioplasty. 相似文献
924.
Ryohei Koyama Mitsuhiro Sanada Hiromichi Itoh Michio Kanechi Noboru Inagaki Yuichi Uno 《Plant Cell, Tissue and Organ Culture》2012,108(2):221-227
Lettuce tipburn is an irreversible physiological disorder caused by calcium deficiency that decreases the crop value. Breeding
a tipburn-resistant cultivar is the only causal therapy in many cases. In this study, we investigated an efficient method
to evaluate lettuce resistance to tipburn in vitro. Seedlings of 19 lettuce cultivars representing three head types were cultured
on agar medium containing EGTA, which chelates Ca2+. The percentage of tipburned leaves decreased proportionally with EGTA concentration. Susceptible cultivars were distinguished
at 0.01 mM EGTA, whereas resistant cultivars were classified at 1.0 mM EGTA. Based on mean values of tipburn measurements,
tipburn susceptibility was highest for ‘Leaf Lettuce’, followed by ‘Butterhead Lettuce’, and then ‘Crisphead Lettuce’. Two
cultivars were selected for further tests using hydroponic and pot culture. The rank order of susceptibility to tipburn in
these experiments was consistent with that of the in vitro assay. The in vitro evaluation of lettuce susceptibility to calcium
deficiency is useful for initial screening of lettuce cultivars against tipburn incidence. Resistant cultivars identified
in this study are practical candidates for cultivation in controlled environments, such as a plant factory, while sensitive
cultivars are also useful as indicator plants to monitor environmental conditions. 相似文献
925.
926.
Gotoh M Fujiwara Y Yue J Liu J Lee S Fells J Uchiyama A Murakami-Murofushi K Kennel S Wall J Patil R Gupte R Balazs L Miller DD Tigyi GJ 《Biochemical Society transactions》2012,40(1):31-36
LPA (lysophosphatidic acid, 1-acyl-2-hydroxy-sn-glycero-3-phosphate), is a growth factor-like lipid mediator that regulates many cellular functions, many of which are unique to malignantly transformed cells. The simple chemical structure of LPA and its profound effects in cancer cells has attracted the attention of the cancer therapeutics field and drives the development of therapeutics based on the LPA scaffold. In biological fluids, LPA is generated by ATX (autotaxin), a lysophospholipase D that cleaves the choline/serine headgroup from lysophosphatidylcholine and lysophosphatidylserine to generate LPA. In the present article, we review some of the key findings that make the ATX-LPA signalling axis an emerging target for cancer therapy. 相似文献
927.
Tozawa T Itoh K Yaoi T Tando S Umekage M Dai H Hosoi H Fushiki S 《Molecular neurobiology》2012,45(2):287-297
Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms
remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with
the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform,
Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71
and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal
sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse
brain. Affinity chromatography with this antibody and the consecutive LC-MS/MS analysis on the interacting proteins revealed
that Dp40 was abundantly expressed in synaptic vesicles and interacted with a group of presynaptic proteins, including syntaxin1A
and SNAP25, which are involved in exocytosis of synaptic vesicles in neurons. We thus suggest that Dp40 may form a novel protein
complex and play a crucial role in presynaptic function. Further studies on these aspects of Dp40 function might provide more
insight into the molecular mechanisms of cognitive impairment found in patients with DMD. 相似文献
928.
Miyake A Nihno S Murakoshi Y Satsuka A Nakayama Y Itoh N 《Mechanisms of development》2012,128(11-12):577-590
Wnt signaling plays crucial roles in neural development. We previously identified Neucrin, a neural-specific secreted antagonist of canonical Wnt/β-catenin signaling, in humans and mice. Neucrin has one cysteine-rich domain, in which the positions of 10 cysteine residues are similar to those in the second cysteine-rich domain of Dickkopfs, secreted Wnt antagonists. Here, we have identified zebrafish neucrin to understand its roles in vivo. Zebrafish Neucrin also has one cysteine-rich domain, which is significantly similar to that of mouse Neucrin. Zebrafish neucrin was also predominantly expressed in developing neural tissues. To examine roles of neucrin in neural development, we analyzed neucrin knockdown embryos. Neural development in zebrafish embryos was impaired by the knockdown of neucrin. The knockdown of neucrin caused increased expression of the Wnt/β-catenin target genes. In contrast, overexpression of neucrin reduced the expression of the Wnt/β-catenin target genes. The knockdown of neucrin affected specification of dorsal region in the midbrain and hindbrain. The knockdown of neucrin also suppressed neuronal differentiation and caused increased cell proliferation and apoptosis in developing neural tissues. Neucrin is a unique secreted Wnt antagonist that is predominantly expressed in developing neural tissues and plays roles in neural development in zebrafish. 相似文献
929.
930.
Zhao Y Nakagawa T Itoh S Inamori K Isaji T Kariya Y Kondo A Miyoshi E Miyazaki K Kawasaki N Taniguchi N Gu J 《The Journal of biological chemistry》2006,281(43):32122-32130
N-acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of beta1,6-GlcNAc branching of N-glycans, which contributes to metastasis. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of a bisecting GlcNAc structure in N-glycans, resulting in the suppression of metastasis. It has long been hypothesized that the suppression of GnT-V product formation by the action of GnT-III would also exist in vivo, which will consequently lead to the inhibition of biological functions of GnT-V. To test this, we draw a comparison among MKN45 cells, which were transfected with GnT-III, GnT-V, or both, respectively. We found that alpha3beta1 integrin-mediated cell migration on laminin 5 was greatly enhanced in the case of GnT-V transfectant. This enhanced cell migration was significantly blocked after the introduction of GnT-III. Consistently, an increase in bisected GlcNAc but a decrease in beta1,6-GlcNAc-branched N-glycans on integrin alpha3 subunit was observed in the double transfectants of GnT-III and GnT-V. Conversely, GnT-III knockdown resulted in increased migration on laminin 5, concomitant with an increase in beta1,6-GlcNAc-branched N-glycans on the alpha3 subunit in CHP134 cells, a human neuroblastoma cell line. Therefore, in this study, the priority of GnT-III for the modification of the alpha3 subunit may be an explanation for why GnT-III inhibits GnT-V-induced cell migration. Taken together, our results demonstrate for the first time that GnT-III and GnT-V can competitively modify the same target glycoprotein and furthermore positively or negatively regulate its biological functions. 相似文献