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151.
Yuji Amano Kazuhisa Yoshino Katsuhiko Kojima Toshikazu Takeshita 《Biochemical and biophysical research communications》2013
Cell surface receptors ubiquitylated after ligand stimulation are internalized and delivered to the lysosomal pathway for degradation. Ubiquitylated receptors are captured by ESCRT protein complexes that sort them to the lysosomal pathway. Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a component of endosomal sorting complexes required for transport (ESCRT)-0 that recognizes ubiquitin attached to receptors, indicating that it functions as a key molecule for ubiquitin-dependent endosomal sorting. In a previous study on interleukin (IL)-2 receptor β (IL-2Rβ) and IL-4 receptor α (IL-4Rα), which are constitutively internalized without ligand stimulation, we revealed that Hrs bound to IL-2Rβ and IL-4Rα in a ubiquitin-independent manner, and identified a hydrophobic amino acid cluster in the cytoplasmic region of IL-2Rβ and IL-4Rα as the Hrs-interacting domain. However, a chimeric receptor containing the hydrophobic amino acid cluster inserted into the C-terminal of IL-2Rα was not delivered to late endosomes, but recycled back to the plasma membrane. In the present study, we explored the functional domain related to endosomal sorting in IL-2Rβ together with the hydrophobic amino acid cluster, and discovered the importance of an approximately 30-amino acid stretch following the C-terminus of the hydrophobic amino acid cluster in IL-2Rβ. Even though the amino acid stretch following the hydrophobic amino acid cluster was composed of arbitrary amino acids, such a stretch was also permissive for the sorting ability, suggesting that the hydrophobic amino acid cluster functions as an endosomal sorting signal. These findings clarify part of the molecular mechanism underlying the ubiquitin-independent endosomal sorting of cytokine receptors that are constitutively internalized without ligand stimulation. 相似文献
152.
Oxidative damage associated with obesity is prevented by overexpression of CuZn- or Mn-superoxide dismutase 总被引:1,自引:0,他引:1
Yuhong Liu Wenbo Qi Arlan Richardson Holly Van Remmen Yuji Ikeno Adam B. Salmon 《Biochemical and biophysical research communications》2013
The development of insulin resistance is the primary step in the etiology of type 2 diabetes mellitus. There are several risk factors associated with insulin resistance, yet the basic biological mechanisms that promote its development are still unclear. There is growing literature that suggests mitochondrial dysfunction and/or oxidative stress play prominent roles in defects in glucose metabolism. Here, we tested whether increased expression of CuZn-superoxide dismutase (Sod1) or Mn-superoxide dismutase (Sod2) prevented obesity-induced changes in oxidative stress and metabolism. Both Sod1 and Sod2 overexpressing mice were protected from high fat diet-induced glucose intolerance. Lipid oxidation (F2-isoprostanes) was significantly increased in muscle and adipose with high fat feeding. Mice with increased expression of either Sod1 or Sod2 showed a significant reduction in this oxidative damage. Surprisingly, mitochondria from the muscle of high fat diet-fed mice showed no significant alteration in function. Together, our data suggest that targeting reduced oxidative damage in general may be a more applicable therapeutic target to prevent insulin resistance than is improving mitochondrial function. 相似文献
153.
Of the 19 strains of Rhizopus delemar deposited as Rhizopus oryzae, seven of them, NBRC 4726, NBRC 4734, NBRC 4746, NBRC 4754, NBRC 4773, NBRC 4775, and NBRC 4801, completely hydrolyzed exogenous sucrose and fructooligosaccharides. The sucrose-hydrolyzing enzyme was purified from the culture filtrate of R. delemar NBRC 4754 and classified to β-fructofuranosidase, similar to that of Amylomyces rouxii CBS 438.76. Fragments including β-fructofuranosidase genes (sucA) of seven strains of R. delemar and A. rouxii CBS 438.76 were amplified and sequenced by PCR with degenerated primers synthesized on the basis of the internal amino acid sequences of purified enzymes and successive inverse PCR. Nucleotide sequences of the obtained fragments revealed that open reading frames of 1,569 bp have no intron and encode 522 amino acids. The presumed proteins contained the typical domain of the glycoside hydrolase 32 family, including β-fructofuranosidase, inulinase, levanase, and fructosyltransferases. Amino acid sequences of SucA proteins from the seven strains of R. delemar were identical and showed 90.0 % identity with those of A. rouxii CBS 438.76. A dendrogram constructed from these amino acid sequences showed that SucA proteins are more closely related to yeast β-fructofuranosidases than to other fungal enzymes. 相似文献
154.
Yuusuke Tamura Kyouhei Hayashi Naoki Omori Yuji Nishiura Kana Watanabe Nobuyuki Tanaka Masahiko Fujioka Naoki Kouyama Akira Yukimasa Yukari Tanaka Takeshi Chiba Hideki Tanioka Hirohide Nambu Hideo Yukioka Hiroki Sato Takayuki Okuno 《Bioorganic & medicinal chemistry letters》2013,23(1):90-95
Optimization of HTS hit 1 for NPY Y5 receptor binding affinity, CYP450 inhibition, solubility and metabolic stability led to the identification of some orally available oxygen-linker derivatives for in vivo study. Among them, derivative 4i inhibited food intake induced by the NPY Y5 selective agonist, and chronic oral administration of 4i in DIO mice caused a dose-dependent reduction of body weight gain. 相似文献
155.
Takako Aboshi Nobuhiro Shimizu Yuji Nakajima Yoshiyuki Honda Yasumasa Kuwahara Hiroshi Amano Naoki Mori 《Insect biochemistry and molecular biology》2013,43(11):991-996
We report here that Tyrophagus similis and Tyrophagus putrescentiae (Astigmata: Acaridae) have the ability to biosynthesize linoleic acid [(9Z, 12Z)-9, 12-octadecadienoic acid] via a Δ12-desaturation step, although animals in general and vertebrates in particular appear to lack this ability. When the mites were fed on dried yeast enriched with d31-hexadecanoic acid (16:0), d27-octadecadienoic acid (18:2), produced from d31-hexadecanoic acid through elongation and desaturation reactions, was identified as a major fatty acid component of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in the mites. The double bond position of d27-octadecadienoic acid (18:2) of PCs and PEs was determined to be 9 and 12, respectively by dimethyldisulfide (DMDS) derivatization. Furthermore, the GC/MS retention time of methyl 9, 12-octadecadienoate obtained from mite extracts agreed well with those of authentic linoleic acid methyl ester. It is still unclear whether the mites themselves or symbiotic microorganisms are responsible for inserting a double bond into the Δ12 position of octadecanoic acid. However, we present here the unique metabolism of fatty acids in the mites. 相似文献
156.
Kenji Sugimoto Kosuke Tamura Chihiro Tohda Naoki Toyooka Hideo Nemoto Yuji Matsuya 《Bioorganic & medicinal chemistry》2013,21(15):4459-4471
As an extended study on development of anti-Alzheimer’s disease agent, we newly synthesized various dihydrofuran-fused perhydrophenanthrenes via o-quinodimethane chemistry. This study revealed that the introduction of carbon side-chain on 8-position or removal of the acetal moiety on 3-position arose a cytotoxicity on rat cortical neurons. On the other hand, the ethereal or thio-ethereal substituent on 8-position enhanced the elongation effect on Aβ-damaged neurons. The necessity of the cyano group on 10b position was also proved in this structure–activity-relationship study. 相似文献
157.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
158.
Keiju Okano Takeshi Nakamura Yuji Kamiya Susumu Ikegami 《Bioscience, biotechnology, and biochemistry》2013,77(3):805-807
Cultured crown gall cells of Catharanthus roseus Don (Vinca rosea L.) was found to contain brassinosteroids. These were identified as brassinolide and castasterone by GC/MS. This is the first conclusive identification of endogenous brassinosteroids in cultured cells. 相似文献
159.
Kojiro Wada Yuji Enomoto Katsura Munakata 《Bioscience, biotechnology, and biochemistry》2013,77(6):946-953
Shiromodiol-diacetate, shiromool, and shiromodiol-monoacetate are insect feeding inhibitors isolated from Parabenzoin trilobum Nakai. On the bases of chemical and spectral evidence we deduced that these compounds have the structure shown in I, XVIII, and XI, respectively. 相似文献
160.
Yuji Koide Mamoru Honma Tokuji Shimomura 《Bioscience, biotechnology, and biochemistry》2013,77(3):775-776
Modified fungal product 4-O-methylascochlorin (MAC) is an experimental agent affecting lipid and carbohydrate metabolism in mammals. The hypocholesterolemic properties of MAC were studied using rats fed on a standard laboratory diet. Because of the insolubility in water, reproducibility of the hypocholesterolemic activity had usually been poor for rats fed ad libitum. The difficulty was overcome by controlled reverse-phase feeding; MAC significantly lowered serum total cholesterol (s-TC) in rats only when given by gastric intubation soon after diet intake.MAC increased fecal excretion of neutral and acidic sterols and also increased biliary flow accompanying increments in biliary cholesterol, bile acids and phospholipids. A much larger increase in neutral sterols was characteristic for MAC. However, intestinal absorption of cholesterol and cholic acid was unaffected by MAC. Three mechanisms therefore seemed to be working in hypocholesterolemic activity: (a) withdrawal of hepatic cholesterol into bile, (b) a larger fecal loss of sterols following increment of biliary sterols and (c) enhanced bile acid synthesis compensating the larger fecal loss. A negative sterol balance often leads to an increase in hepatic cholesterogenesis. However, cholesterogenesis, as judged from incorporation of the precursors, was unchanged by MAC. 相似文献