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991.
Shin Miura Shin Hamada Atsushi Masamune Kennichi Satoh Tooru Shimosegawa 《Experimental cell research》2014
The prognosis of pancreatic cancer is dismal due to the frequent metastasis and invasion to surrounding organs. Numerous molecules are involved in the malignant behavior of pancreatic cancer cells, but the entire process remains unclear. Several reports have suggested that CUB-domain containing protein-1 (CDCP1) is highly expressed in pancreatic cancer, but its impact on the invasive growth and the upstream regulator remain elusive. To clarify the role of CDCP1 in pancreatic cancer, we here examined the effects of CDCP1 knockdown on the cell behaviors of pancreatic cancer cells. Knockdown of CDCP1 expression in Panc-1 resulted in reduced cellular migration accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin. Knockdown of CDCP1 attenuated the spheroid formation and resistance against gemcitabine, which are some of the cancer stem cell-related phenotypes. Bone morphogenetic protein 4 (BMP4) was found to induce CDCP1 expression via the extracellular signal regulated kinase pathway, suggesting that CDCP1 has a substantial role in the BMP4-induced epithelial-mesenchymal transition. These results indicate that CDCP1 represses the epithelial phenotype of pancreatic cancer cells. 相似文献
992.
Masayuki Sakiyama Hirotaka Matsuo Seiko Shimizu Toshinori Chiba Akiyoshi Nakayama Yuzo Takada Takahiro Nakamura Tappei Takada Emi Morita Mariko Naito Kenji Wakai Hiroki Inoue Seishiro Tatsukawa Junki Sato Kazumi Shimono Toshiaki Makino Takahiro Satoh Hiroshi Suzuki Yoshikatsu Kanai Nobuyuki Hamajima Yutaka Sakurai Kimiyoshi Ichida Toru Shimizu Nariyoshi Shinomiya 《Human cell》2014,27(1):1-4
Gout is a common disease resulting from hyperuricemia which causes acute arthritis. Recently, genome-wide association studies revealed an association between serum uric acid levels and a common variant of leucine-rich repeat-containing 16A (LRRC16A) gene. However, it remains to be clarified whether LRRC16A contributes to the susceptibility to gout. In this study, we investigated the relationship between rs742132 in LRRC16A and gout. A total of 545 Japanese male gout cases and 1,115 male individuals as a control group were genotyped. rs742132 A/A genotype significantly increased the risk of gout, conferring an odds ratio of 1.30 (95 % CI 1.05–1.60; p = 0.015). LRRC16A encodes a protein called capping protein ARP2/3 and myosin-I linker (CARMIL), which serves as an inhibitor of the actin capping protein (CP). CP is an essential element of the actin cytoskeleton, which binds to the barbed end of the actin filament and regulates its polymerization. In the apical membrane of proximal tubular cells in the human kidney, the urate-transporting multimolecular complex (urate transportsome) is proposed to consist of several urate transporters and scaffolding proteins, which interact with the actin cytoskeleton. Thus, if there is a CARMIL dysfunction and regulatory disability in actin polymerization, urate transportsome may be unable to operate appropriately. We have shown for the first time that CARMIL/LRRC16A was associated with gout, which could be due to urate transportsome failure. 相似文献
993.
Beng Hui Tan Yasutsugu Suzuki Hirotaka Takahashi Pamela Ho Rui Ying Chikako Takahashi Qi'En Han Wei Xin Chin Sheng-Hao Chao Tatsuya Sawasaki Naoki Yamamoto Youichi Suzuki 《The Journal of biological chemistry》2014,289(38):26368-26382
Integration, one of the hallmarks of retrovirus replication, is mediated by a nucleoprotein complex called the preintegration complex (PIC), in which viral DNA is associated with many protein components that are required for completion of the early phase of infection. A striking feature of the PIC is its powerful integration activity in vitro. The PICs from a freshly isolated cytoplasmic extract of infected cells are able to insert viral DNA into exogenously added target DNA in vitro. Therefore, a PIC-based in vitro assay is a reliable system for assessing protein factors influencing retroviral integration. In this study, we applied a microtiter plate-based in vitro assay to a screening study using a protein library that was produced by the wheat germ cell-free protein synthesis system. Using a library of human E3 ubiquitin ligases, we identified RFPL3 as a potential stimulator of human immunodeficiency virus, type 1 (HIV-1) PIC integration activity in vitro. This enhancement of PIC activity by RFPL3 was likely to be attributed to its N-terminal RING domain. To further understand the functional role of RFPL3 in HIV infection, we created a human cell line overexpressing RFPL3. Immunoprecipitation analysis revealed that RFPL3 was associated with the human immunodeficiency virus, type 1 PICs in infected cells. More importantly, single-round HIV-1 infection was enhanced significantly by RFPL3 expression. Our proteomic approach displays an advantage in the identification of new cellular proteins affecting the integration activity of the PIC and, therefore, contributes to the understanding of functional interaction between retroviral integration complexes and host factors. 相似文献
994.
995.
Mai Thi Nhu Tran Junko Tanaka Michito Hamada Yuka Sugiyama Shota Sakaguchi Megumi Nakamura Satoru Takahashi Yoshihiro Miwa 《Experimental Animals》2014,63(3):311-319
Fluorescent proteins with light wavelengths within the optical window are one of the
improvements in in vivo imaging techniques. Near-infrared (NIR)
fluorescent protein (iRFP) is a stable, nontoxic protein that emits fluorescence within
the NIR optical window without the addition of exogenous substrate. However, studies
utilizing an in vivo iRFP model have not yet been published. Here, we
report the generation of transgenic iRFP mice with ubiquitous NIR fluorescence expression.
iRFP expression was observed in approximately 50% of the offspring from a matings between
iRFP transgenic and WT mice. The serum and blood cell indices and body weights of iRFP
mice were similar to those of WT mice. Red fluorescence with an excitation wavelength of
690 nm and an emission wavelength of 713 nm was detected in both newborn and adult iRFP
mice. We also detected fluorescence emission in whole organs of the iRFP mice, including
the brain, heart, liver, kidney, spleen, lung, pancreas, bone, testis, thymus, and adipose
tissue. Therefore, iRFP transgenic mice may therefore be a useful tool for various types
of in vivo imaging. 相似文献
996.
997.
Tappei Takada Kimiyoshi Ichida Hirotaka Matsuo Akiyoshi Nakayama Keizo Murakami Yoshihide Yamanashi 《Nucleosides, nucleotides & nucleic acids》2014,33(4-6):275-281
ATP-binding cassette transporter G2 (ABCG2), also known as breast cancer resistance protein (BCRP), is identified as a high-capacity urate exporter and its dysfunction has an association with serum uric acid (SUA) levels and gout/hyperuricemia risk. However, pathophysiologically important pathway(s) responsible for the ABCG2-mediated urate excretion were unknown. In this study, we investigated how ABCG2 dysfunction affected the urate excretion pathways. First, we revealed that mouse Abcg2 mediates urate transport using the membrane vesicle system. The export process by mouse Abcg2 was ATP-dependent and not saturable under the physiological concentration of urate. Then, we characterized the excretion of urate into urine, bile, and intestinal lumen using in vivo mouse model. SUA of Abcg2-knockout mice was significantly higher than that of control mice. Under this condition, the renal urate excretion was increased in Abcg2-knockout mice, whereas the urate excretion from the intestine was decreased to less than a half. Biliary urate excretion showed no significant difference regardless of Abcg2 genotype. From these results, we estimated the relative contribution of each pathway to total urate excretion; in wild-type mice, the renal excretion pathway contributes approximately two-thirds, the intestinal excretion pathway contributes one-third of the total urate excretion, and the urate excretion into bile is minor. Decreased intestinal excretion could account for the increased SUA of Abcg2-knockout mice. Thus, ABCG2 is suggested to have an important role in extra-renal urate excretion, especially in intestinal excretion. Accordingly, increased SUA in patients with ABCG2 dysfunction could be explained by the decreased excretion of urate from the intestine. 相似文献
998.
Masaya Yamaguchi Yutaka Terao Taiji Ogawa Shigeyuki Hamada 《Biochemical and biophysical research communications》2009,390(1):155-160
Streptococcus pneumoniae is a major pathogen of community-acquired pneumonia and one of its major virulence factors is pneumolysin, which functions as a cholesterol-dependent cytolytic pore-forming toxin. In this study, we identified the ply-like gene spd0729 in a BLAST search. Unexpectedly, hemolytic and cytotoxic assays showed no significant differences between a Δspd0729 mutant strain and the wild-type strain, whereas the mutant strain exhibited weaker anti-phagocytic activity in human peripheral blood. In addition, real-time RT-PCR analysis revealed that four capsular biosynthesis genes in the mutant strain had expressions 7- to 432-fold greater than those of the wild type, while an enzyme-linked immunoassay showed a mean 3-fold greater amount of total capsular polysaccharide in the mutant strain. These results suggest that Spd0729 is not a cytolysin, though it plays crucial roles in anti-phagocytosis and regulation of capsule expression. Thus, we named Spd0729 as a negative regulator of capsular polysaccharide synthesis (Nrc). 相似文献
999.
1000.
Hirotaka Imai Nao Hakkaku Ryo Iwamoto Jyunko Suzuki Toshiyuki Suzuki Yoko Tajima Kumiko Konishi Shintaro Minami Shizuko Ichinose Kazuhiro Ishizaka Seiji Shioda Satoru Arata Masuhiro Nishimura Shinsaku Naito Yasuhito Nakagawa 《The Journal of biological chemistry》2009,284(47):32522-32532
Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an intracellular antioxidant enzyme that directly reduces peroxidized phospholipids. GPx4 is strongly expressed in the mitochondria of testis and spermatozoa. We previously found a significant decrease in the expression of GPx4 in spermatozoa from 30% of infertile human males diagnosed with oligoasthenozoospermia (Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001) Biol. Reprod. 64, 674–683). To clarify whether defective GPx4 in spermatocytes causes male infertility, we established spermatocyte-specific GPx4 knock-out mice using a Cre-loxP system. All the spermatocyte-specific GPx4 knock-out male mice were found to be infertile despite normal plug formation after mating and displayed a significant decrease in the number of spermatozoa. Isolated epididymal GPx4-null spermatozoa could not fertilize oocytes in vitro. These spermatozoa showed significant reductions of forward motility and the mitochondrial membrane potential. These impairments were accompanied by the structural abnormality, such as a hairpin-like flagella bend at the midpiece and swelling of mitochondria in the spermatozoa. These results demonstrate that the depletion of GPx4 in spermatocytes causes severe abnormalities in spermatozoa. This may be one of the causes of male infertility in mice and humans. 相似文献