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141.
In the developing nervous system, functional neural networks are constructed with intricate coordination of neuronal migrations and axonal projections. We have previously reported a ventral tangential migration of a special type of cortical neurons, lot cells, in the mouse embryo. These neurons originate from the ventricular zone of the entire neocortex, tangentially migrate in the surface layer of the neocortex into the ventral direction, align in the future pathway of the lateral olfactory tract (LOT) and eventually guide the projection of LOT axons. In this study, we developed an organotypic culture system to investigate the regulation of this cell migration in the developing telencephalon. Our data show that the neocortex contains the signals that direct lot cells ventrally, that the ganglionic eminence excludes lot cells by repelling the migration and that lot cells are attracted to netrin 1, an axon guidance factor. Furthermore, we demonstrate that mutations in the genes encoding netrin 1 and its functional receptor Dcc lead to inappropriate distribution of lot cells and subsequent partial disruption of LOT projection. These results suggest that netrin 1 regulates the migration of lot cells and LOT projections, possibly by ensuring the correct distribution of these guidepost neurons. 相似文献
142.
Kurokawa Masatoshi Sato Fuminori Aramaki Shinya Soh Tomoki Yamauchi Nobuhiko Hattori Masa-aki 《Molecular and cellular biochemistry》2009,322(1-2):193-206
Molecular and Cellular Biochemistry - Viral inflammation and infection of mesothelial cells (MC) are a major problem in several organ systems including pleura, pericardium and peritoneum. Toll-like... 相似文献
143.
Hirofumi Sakamoto Tomomi Kuboi Takahiko Nagakura Sayako Hayashi Fumio Hoshi Kenichiro Mutoh Kiyotaka Watanabe Koichi Orino 《Biometals》2009,22(5):793-802
Ferritin-binding proteins (FBPs) such as anti-ferritin antibody, α-2-macroglobulin, apolipoprotein B are expected to interact
with circulating ferritin to eliminate it from circulation. However, we found that feline serum more strongly inhibits the
detection of canine liver ferritin by immunoassay than its apoferritin; putative FBPs probably conceal ferritin epitopes detected
by anti-ferritin antibodies. After complex formation between affinity-purified FBPs and canine liver ferritin, co-immunoprecipitates
of the complex by anti-bovine spleen ferritin antibody were found to contain autoantibodies (IgG, IgM, and IgA) to ferritin
by immunoblot analysis with antibodies specific for feline IgG, IgM, and IgA. On the other hand, affinity-purified samples
did not show any inhibitory effect in the ferritin immunoassay. This result shows that feline serum has another FBP, which
inhibits ferritin immunoassays, but not anti-ferritin autoantibody. A feline FBP was partially purified from feline serum
by (NH4)2SO4 fractionation (33–50%), gel filtration chromatography, and anion exchange chromatography. After binding of the partially
purified sample with canine liver ferritin coupled-Sepharose gel, the FBP was separated and purified from complexes formed
in a native-PAGE gel. SDS–PAGE analysis showed that the purified FBP is a homomultimer composed of 31 kDa monomeric subunits
connected by intermolecular disulfide bonds. Detection of feline liver ferritin by immunoassay was inhibited by FBP in a dose-dependent
manner. The purified protein molecules appeared to be conglomerate of pentraxin-like molecules by its electron micrographic
appearance. These results demonstrate that feline serum contains a novel FBP as inhibitory factor of ferritin immunoassay
with different molecular properties from those of other mammalian FBPs, in addition to auto-antibodies (IgG, IgM, and IgA)
to ferritin. 相似文献
144.
Johnson RJ Sautin YY Oliver WJ Roncal C Mu W Gabriela Sanchez-Lozada L Rodriguez-Iturbe B Nakagawa T Benner SA 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2009,179(1):67-76
Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively
unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has
been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a
pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this
paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting.
We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid
stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate
synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging
“survival” response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual
development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich
foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular
disease in today’s society.
Disclaimers Dr Johnson is listed as an inventor on several patent applications related to the role of uric acid in hypertension and metabolic
syndrome; Dr Johnson is also an author for a book on fructose and uric acid (The Sugar Fix) that was published by Rodale in
2008. 相似文献
145.
Yuki Kawakami Tomomi Nakamura Tomoko Hosokawa Toshiko Suzuki-Yamamoto Hiromi Yamashita Masumi Kimoto Hideaki Tsuji Hideki Yoshida Takahiko Hada Yoshitaka Takahashi 《Prostaglandins, leukotrienes, and essential fatty acids》2009,80(5-6):239-245
Prostaglandin endoperoxide H synthase (PGHS) is a key enzyme for the synthesis of prostaglandins (PGs) which play important roles in inflammation and carcinogenesis. Because the extract from Psidium guajava is known to have a variety of beneficial effects on our body including the anti-inflammatory, antioxidative and antiproliferative activities, we investigated whether the extract inhibited the catalytic activity of the two PGHS isoforms using linoleic acid as an alternative substrate. The guava leaf extract inhibited the cyclooxygenase reaction of recombinant human PGHS-1 and PGHS-2 as assessed by conversion of linoleic acid to 9- and 13-hydroxyoctadecadienoic acids (HODEs). The guava leaf extract also inhibited the PG hydroperoxidase activity of PGHS-1, which was not affected by nonsteroidal anti-inflammatory drugs (NSAIDs). Quercetin which was one of the major components not only inhibited the cyclooxygenase activity of both isoforms but also partially inhibited the PG hydroperoxidase activity. Overexpression of human PGHS-1 and PGHS-2 in the human colon carcinoma cells increased the DNA synthesis rate as compared with mock-transfected cells which did not express any isoforms. The guava leaf extract not only inhibited the PGE2 synthesis but also suppressed the DNA synthesis rate in the PGHS-1- and PGHS-2-expressing cells to the same level as mock-transfected cells. These results demonstrate the antiproliferative activity of the guava leaf extract which is at least in part caused by inhibition of the catalytic activity of PGHS isoforms. 相似文献
146.
Takahiko Seto Toshiro Takai Nobuyuki Ebihara Xiao-Ling Wang Hideoki Ogawa Ko Okumura 《Biochemical and biophysical research communications》2009,379(3):681-106
House dust mites are a major source of allergens associated with allergic diseases including allergic conjunctivitis. Here, we demonstrate that mite-derived serine protease activity induces the release of cytokines from human ocular conjunctival epithelial cells in vitro and innate antiproteases, secretory leukocyte protease inhibitor (SLPI) and α1-antitrypsin, can inhibit the response. An extract prepared from a whole-mite culture induced the release of IL-6 and IL-8 and upregulated their gene expression in the human conjunctival epithelial cell line Chang, responses which were inhibited not only by a synthetic serine protease-specific inhibitor, AEBSF, but also by SLPI and α1-antitrypsin at a physiologically relevant concentration. The findings suggest a homeostatic role for SLPI and α1-antitrypsin against the proteases contained in allergen sources in the ocular conjunctiva and that exposure to house dust particles containing mite-derived serine protease activity could be involved in the initiation of sensitization through the ocular conjunctival epithelium and/or exacerbation of allergic conjunctivitis. 相似文献
147.
Tomohiko Urano Takahiko Usui Shizu Takeda Atsushi Okada Yoshiko Ishida Jun Otomo Satoshi Inoue 《Biochemical and biophysical research communications》2009,383(2):263-251
Terf/TRIM17 is a member of the TRIM family of proteins, which is characterized by the RING finger, B-box, and coiled-coil domains. In the present study, we found that terf interacts with TRIM44. Terf underwent ubiquitination in vitro in the presence of the E2 enzyme UbcH6; this suggests that terf exhibits E3 ubiquitin ligase activity. It was also found that terf was conjugated with polyubiquitin chains and stabilized by the proteasome inhibitor in mammalian cells; this suggested that terf rendered itself susceptible to proteasomal degradation through polyubiquitination. We also found that TRIM44 inhibited ubiquitination of terf, and thus stabilized the protein. The N-terminal region of TRIM44 contains a zinc-finger domain found in ubiquitin hydrolases (ZF UBP) and ubiquitin specific proteases (USPs). Thus, we proposed that TRIM44 may function as a new class of the “USP-like-TRIM” which regulates the activity of associated TRIM proteins. 相似文献
148.
Hisashi Hashimoto Rieko Miyamoto Naoki Watanabe Dai Shiba Kenjiro Ozato Chikako Inoue Yuko Kubo Akihiko Koga Tomoko Jindo Takanori Narita Kiyoshi Naruse Kazuko Ohishi Keiko Nogata Tadasu Shin-I Shuichi Asakawa Nobuyoshi Shimizu Tomotsune Miyamoto Toshio Mochizuki Takahiko Yokoyama Hiroshi Hori Hiroyuki Takeda Yuji Kohara Yuko Wakamatsu 《PloS one》2009,4(7)
Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients. 相似文献
149.
Hiroyasu Konno Takuya Yamamoto Kohsuke Yamazaki Jin Gohda Taishin Akiyama Kentaro Semba Hideo Goto Atsushi Kato Toshiaki Yujiri Takahiko Imai Yasushi Kawaguchi Bing Su Osamu Takeuchi Shizuo Akira Yasuko Tsunetsugu-Yokota Jun-ichiro Inoue 《PloS one》2009,4(5)
Background
In response to viral infection, the innate immune system recognizes viral nucleic acids and then induces production of proinflammatory cytokines and type I interferons (IFNs). Toll-like receptor 7 (TLR7) and TLR9 detect viral RNA and DNA, respectively, in endosomal compartments, leading to the activation of nuclear factor κB (NF-κB) and IFN regulatory factors (IRFs) in plasmacytoid dendritic cells. During such TLR signaling, TNF receptor-associated factor 6 (TRAF6) is essential for the activation of NF-κB and the production of type I IFN. In contrast, RIG-like helicases (RLHs), cytosolic RNA sensors, are indispensable for antiviral responses in conventional dendritic cells, macrophages, and fibroblasts. However, the contribution of TRAF6 to the detection of cytosolic viral nucleic acids has been controversial, and the involvement of TRAF6 in IRF activation has not been adequately addressed.Principal Findings
Here we first show that TRAF6 plays a critical role in RLH signaling. The absence of TRAF6 resulted in enhanced viral replication and a significant reduction in the production of IL-6 and type I IFNs after infection with RNA virus. Activation of NF-κB and IRF7, but not that of IRF3, was significantly impaired during RLH signaling in the absence of TRAF6. TGFβ-activated kinase 1 (TAK1) and MEKK3, whose activation by TRAF6 during TLR signaling is involved in NF-κB activation, were not essential for RLH-mediated NF-κB activation. We also demonstrate that TRAF6-deficiency impaired cytosolic DNA-induced antiviral responses, and this impairment was due to defective activation of NF-κB and IRF7.Conclusions/Significance
Thus, TRAF6 mediates antiviral responses triggered by cytosolic viral DNA and RNA in a way that differs from that associated with TLR signaling. Given its essential role in signaling by various receptors involved in the acquired immune system, TRAF6 represents a key molecule in innate and antigen-specific immune responses against viral infection. 相似文献150.
Takashi Nagashima Takahiko Aoyama Akiko Fukasawa Satoshi Watabe Noboru Fukuda Takahiro Ueno Hiroshi Sugiyama Hiroki Nagase Yoshiaki Matsumoto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2009,877(11-12):1070-1076
Pyrrole (Py)–imidazole (Im) polyamides synthesized by combining N-methylpyrrole and N-methylimidazole amino acids have been identified as novel candidates for gene therapy. In this study, a sensitive method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with an electrospray ionization (ESI) source was developed and validated for the determination and quantification of Py–Im polyamide in rat plasma. Py–Im polyamide was extracted from rat plasma by solid-phase extraction (SPE) using a Waters Oasis® HLB cartridge. Separation was achieved on an ACQUITY UPLC HSS T3 (1.8 μm, 2.1 × 50 mm) column by gradient elution using acetonitrile:distilled water:acetic acid (5:95:0.1, v/v/v) and acetonitrile:distilled water:acetic acid (95:5:0.1, v/v/v). The method was validated over the range of 10–1000 ng/mL and the lower limit of quantification (LLOQ) was 10 ng/mL. This method was successfully applied to the investigation of the pharmacokinetics of Py–Im polyamide after intravenous administration. 相似文献