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51.
Hanada S Harada M Abe M Akiba J Sakata M Kwan R Taniguchi E Kawaguchi T Koga H Nagata E Ueno T Sata M 《The journal of histochemistry and cytochemistry》2012,60(6):475-483
Mallory-Denk bodies (MDBs) are hepatocyte cytoplasmic inclusions found in several liver diseases and consist primarily of the cytoskeletal proteins, keratins 8 and 18 (K8/K18). Recent evidence indicates that the extent of stress-induced protein misfolding, a K8>K18 overexpression state, and transglutaminase-2 activation promote MDB formation. In addition, the genetic background and gender play an important role in mouse MDB formation, but the effect of aging on this process is unknown. Given that oxidative stress increases with aging, the authors hypothesized that aging predisposes to MDB formation. They used an established mouse MDB model-namely, feeding non-transgenic male FVB/N mice (1, 3, and 8 months old) with 3,5 diethoxycarbonyl-1,4-dihydrocollidine for 2 months. MDB formation was assessed using immunofluorescence staining and biochemically by demonstrating keratin and ubiquitin-containing crosslinks generated by transglutaminase-2. Immunofluorescence staining showed that old mice had a significant increase in MDB formation compared with young mice. MDB formation paralleled the generation of high molecular weight ubiquitinated keratin-containing complexes and induction of p62. Old mouse livers had increased oxidative stress. In addition, 20S proteasome activity and autophagy were decreased, and endoplasmic reticulum stress was increased in older livers. Therefore, aging predisposes to experimental MDB formation, possibly by decreased activity of protein degradation machinery. 相似文献
52.
53.
Eisuke Kato Michitsugu Yama Ryo Nakagomi Toshiro Shibata Keizo Hosokawa Jun Kawabata 《Bioorganic & medicinal chemistry letters》2012,22(20):6410-6412
Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-l-threonic acid and 3-O-caffeoyl-4-O-galloyl-l-threonic acid, which can be recognized as a pancreatic lipase’s substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-l-threonic acid, possessed the most potent activity with IC50 value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity. 相似文献
54.
New findings reveal that, in Caenorhabditis elegans embryos, the centrosome provides signals that induce cell polarization, independently of its function as the microtubule-organizing center. 相似文献
55.
A statistical approach was used to characterize the heterogeneous structures of bacterial cellulose samples pretreated with four kinds of ionic liquids (ILs). The structural heterogeneity of these samples was measured by Fourier transform infrared spectroscopy as well as solid-state NMR methods such as cross-polarization magic-angle spinning and dipolar-assisted rotational resonance. The obtained data matrices were then evaluated by principal components analysis. The measured 1-D data clearly revealed the modification of crystalline cellulose; in addition, the statistical approach revealed subtle structural changes that occurred upon pretreatment with different kinds of ILs. To investigate whether such regenerated structural changes occurred because of solubilization, we examined the intermolecular nuclear Overhauser effect between cellulose and an IL. Our results clarify how the nucleophilic imidazole is attacked and suggest that the cation of the IL is associated with the collapse of hydrogen bonds in cellulose. 相似文献
56.
57.
Tanigawa M Miyamoto K Kobayashi S Sato M Akutsu H Okabe M Mekada E Sakakibara K Miyado M Umezawa A Miyado K 《Molecular reproduction and development》2008,75(1):150-155
Tetraspanin CD81 is closely homologous in amino acid sequence with CD9. CD9 is well known to be involved in sperm-egg fusion, and CD81 has also been reported to be involved in membrane fusion events. However, the function of CD81 as well as that of CD9 in membrane fusion remains unclear. Here, we report that disruption of the mouse CD81 gene led to a reduction in the fecundity of female mice, and CD81-/- eggs had impaired ability to fuse with sperm. Furthermore, we demonstrated that when CD81-/- eggs were incubated with sperm, some of the sperm that penetrated into the perivitelline space of CD81-/- eggs had not yet undergone the acrosome reaction, indicating that the impaired fusibility of CD81-/- eggs may be in part caused by failure of the acrosome reaction of sperm. In addition, we showed that CD81 was highly expressed in granulosa cells, somatic cells that surround oocytes. Our observations suggest that there is an interaction between sperm and CD81 on somatic cells surrounding eggs before the direct interaction of sperm and eggs. Our results may provide new clues for clarifying the cellular mechanism of the acrosome reaction, which is required for sperm-egg fusion. 相似文献
58.
Yotsumoto F Yagi H Suzuki SO Oki E Tsujioka H Hachisuga T Sonoda K Kawarabayashi T Mekada E Miyamoto S 《Biochemical and biophysical research communications》2008,365(3):555-561
Aberrant expression levels of epidermal growth factor receptor (EGFR) and its cognate ligands have been recognized as one of the causes of cancer progression. To investigate the validity of EGFR ligands as targets for cancer therapy, we examined the expression of EGFR ligands and in vitro anti-tumor effects of small interference RNA (siRNA) for EGFR ligands in various cancer cells. HB-EGF expression was dominantly elevated in ovarian, gastric, and breast cancer, melanoma and glioblastoma cells, whereas amphiregulin was primarily expressed in pancreatic, colon, and prostate cancer, renal cell carcinoma and cholangiocarcinoma cells. Transfection of siRNAs for HB-EGF or amphiregulin into these cells significantly increased the numbers of apoptotic cells with attenuation of EGFR and ERK activation. In lung cancer cells, any EGFR ligand was not recognized as a validated target for cancer therapy. These results suggest that HB-EGF and amphiregulin are promising targets for cancer therapy. 相似文献
59.
We isolated five polymorphic microsatellite loci from the drepanosiphid aphid Tuberculatus quercicola (Matsumura) that is associated with the Daimyo oak, Quercus dentata Thunberg, using the magnetic particles method. The isolated loci were polymorphic, with four to 16 alleles in 40 aphids. Expected heterozygosities ranged from 0.4 to 0.82. These loci can be used to quantify seasonal changes in clonal diversity in the metapopulation and the extent of clonal mixing in the colonies. 相似文献
60.
Eisuke Sato Maho Morita Haruo Ogawa Masato Iwatsuki Rei Hokari Aki Ishiyama Satoshi Ōmura Arihiro Iwasaki Kiyotake Suenaga 《Bioorganic & medicinal chemistry letters》2018,28(3):298-301
Biselyngbyaside, an 18-membered macrolide glycoside from marine cyanobacteria, and its derivatives are known to be sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors. Recently, a SERCA orthologue of the malaria parasite, PfATP6, has attracted attention as a malarial drug target. To provide a novel drug lead, we designed new synthetic analogs of biselyngbyolide B, the aglycone of biselyngbyaside, based on the co-crystal structure of SERCA with biselyngbyolide B, and synthesized them using the established synthetic route for biselyngbyolide B. Their biological activities against malarial parasites were evaluated. 相似文献