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991.
992.
Ishikawa T Terai S Urata Y Marumoto Y Aoyama K Murata T Mizunaga Y Yamamoto N Nishina H Shinoda K Sakaida I 《Cell and tissue research》2007,327(3):463-470
We previously reported that fibroblast growth factor 2 (FGF2) facilitated the differentiation of transplanted bone marrow
cells (BMCs) into hepatocytes. Our earlier study also demonstrated that administration of FGF2 in combination with bone marrow
transplantation (BMT) synergistically activated tumor necrosis factor-alpha signaling and significantly improved liver function
and prognosis more than BMT alone. However, the way that it affected the extracellular matrix remained unclear. Here, we investigated
the effect of FGF2 treatment together with BMT on liver fibrosis in mice treated with carbon tetrachloride (CCl4). Transplantation of BMCs and concurrent treatment with FGF2 caused a statistically significant reduction in CCl4-induced liver fibrosis that was accompanied by strong expression of matrix metalloproteinase 9 as compared with FGF2-only
treatment or BMT alone. Moreover, in this process, the proliferation of bone-marrow-derived cells was accelerated without
causing apoptosis. Thus, the administration of FGF2 in combination with BMT synergistically improves CCl4-induced liver fibrosis in mice. This treatment has the potential of being an effective therapy for patients with liver cirrhosis.
This study was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (nos. 16390211
and 16590597) and for translational research from the Ministry of Health, Labor and Welfare (H-trans-5 and H17-Special-015). 相似文献
993.
994.
Nishino Y Yamamoto K Kimura S Kikuchi A Shiro Y Iyanagi T 《Archives of biochemistry and biophysics》2007,465(1):254-265
The object of this study was to clarify the mechanism of electron transfer in the human endothelial nitric oxide synthase (eNOS) reductase domain using recombinant eNOS reductase domains; the FAD/NADPH domain containing FAD- and NADPH-binding sites and the FAD/FMN domain containing FAD/NADPH-, FMN-, and a calmodulin-binding sites. In the presence of molecular oxygen or menadione, the reduced FAD/NADPH domain is oxidized via the neutral (blue) semiquinone (FADH(*)), which has a characteristic absorption peak at 520 nm. The FAD/NADPH and FAD/FMN domains have high activity for ferricyanide, but the FAD/FMN domain has low activity for cytochrome c. In the presence or absence of calcium/calmodulin (Ca(2+)/CaM), reduction of the oxidized flavins (FAD-FMN) and air-stable semiquinone (FAD-FMNH(*)) with NADPH occurred in at least two phases in the absorbance change at 457nm. In the presence of Ca(2+)/CaM, the reduction rate of both phases was significantly increased. In contrast, an absorbance change at 596nm gradually increased in two phases, but the rate of the fast phase was decreased by approximately 50% of that in the presence of Ca(2+)/CaM. The air-stable semiquinone form was rapidly reduced by NADPH, but a significant absorbance change at 520 nm was not observed. These findings indicate that the conversion of FADH(2)-FMNH(*) to FADH(*)-FMNH(2) is unfavorable. Reduction of the FAD moiety is activated by CaM, but the formation rate of the active intermediate, FADH(*)-FMNH(2) is extremely low. These events could cause a lowering of enzyme activity in the catalytic cycle. 相似文献
995.
Popp D Yamamoto A Iwasa M Narita A Maeda K Maéda Y 《Biochemical and biophysical research communications》2007,354(1):109-114
Apoptosis is a highly conserved procedure of cell death and occurs under various stimuli, including oxidative stress. A small heat shock protein, alphaB-crystallin, is found to process resistance to apoptosis in some cells and tissues. But the mechanisms under this protective role are not fully understood. In the present study, we reported the early protective role of alphaB-crystallin against hydrogen peroxide-induced apoptosis in mice myogenic C(2)C(12) cells. alphaB-Crystallin interacted with p53, a proapoptotic protein, during cell apoptosis and such protein interaction mainly occurred in the cytoplasm of the cells, suggesting that the interaction of alphaB-crystallin with p53 might prevent the translocation of p53 from cytoplasm to mitochondria. Hence, this study provides a hint that alphaB-crystallin affects on p53 mitochondrial translocation during oxidative stress-induced apoptosis. 相似文献
996.
Kaseda R Iino N Hosojima M Takeda T Hosaka K Kobayashi A Yamamoto K Suzuki A Kasai A Suzuki Y Gejyo F Saito A 《Biochemical and biophysical research communications》2007,357(4):1130-1134
Serum levels of cystatin C, an endogenous cysteine proteinase inhibitor, are often used as an indicator of glomerular filtration rate. Although it is known that cystatin C is filtered by glomeruli and metabolized in proximal tubule cells (PTC), the precise molecular mechanism underlying this process is undetermined. Using quartz-crystal microbalance analyses, we demonstrate that cystatin C binds directly to megalin, an endocytic receptor in PTC, in a Ca(+)-dependent manner. We also find that cystatin C is endocytosed specifically via megalin in rat yolk sac epithelium-derived L2 cells which share a variety of characteristics with PTC. Finally, in vivo studies using kidney-specific megalin knockout mice provide evidence that megalin mediates proximal tubular uptake of cystatin C. We conclude that megalin is an endocytic receptor of cystatin C in PTC. 相似文献
997.
N Ogawa T Yamaguchi S Yano M Yamauchi M Yamamoto T Sugimoto 《Hormones et métabolisme》2007,39(12):871-875
Type 1 diabetes mellitus is known to be associated with reduced bone mass and increased bone fractures. This is thought to be due to a decrease in osteoblastic bone formation rather than an increase in osteoclastic bone resorption, but the precise mechanism is unknown. In this study, we examined whether or not high glucose or advanced glycation end-products (AGEs), which play key roles in the pathogenesis and complications of diabetes, affect the differentiation of osteoblastic MC3T3-E1 cells. First, MC3T3-E1 cells were incubated in media containing either 22 mM glucose, 22 mM mannitol, 300 microg/ml AGE2, or 300 microg/ml AGE3. Each of these agents alone did not affect the mineralization of the cells by von Kossa staining and Alizarin red staining. However, high glucose but not mannitol or AGEs markedly increased mRNA expression of AGE receptor (RAGE) by real-time PCR. Next, we examined the combined effects of high glucose and AGEs on the differentiation of MC3T3-E1 cells. The combination of 22 mM glucose and 300 microg/ml AGE2 significantly inhibited the mineralization of MC3T3-E1 cells, and 22 mM glucose in combination with either 300 microg/ml AGE2 or AGE3 apparently decreased osteocalcin mRNA expression. These results suggest that high glucose or AGEs alone might have no effect on osteoblastic differentiation, but their combination could additionally or synergistically inhibit osteoblastic mineralization through glucose-induced increase in RAGE expression. 相似文献
998.
999.
1000.
We cloned, expressed and characterized a novel alpha/beta-galactoside alpha2,3-sialyltransferase from Vibrio sp. bacterium JT-FAJ-16. Using a alpha2,3-sialyltransferase gene from a marine bacterium as a probe, a DNA sequence encoding a 402-amino-acid protein was identified from the JT-FAJ-16 genomic library. The protein showed 27.3-64.7% identity to the bacterial sialyltransferases classified into glycosyltransferase family 80. The protein showed sialyltransferase activity when expressed in Escherichia coli. The N-terminal truncated form of the enzyme was amplified in E. coli and its recovered activity was 215.7 unit/l culture medium. It was purified as a single band on SDS-PAGE through the three chromatographic steps. The specific activity of the purified recombinant enzyme reached 57.5 unit/mg protein. The alpha2,3sialylation was confirmed by (1)H- and (13)C-NMR analyses of the reaction products. The enzyme was optimally active at pH 5.5 and at 20 degrees C. Interestingly, the enzyme used both the alpha- and beta-anomers of galactosides as acceptors, suggesting that it can be described as an alpha/beta-galactoside alpha2,3-sialyltransferase. The enzyme had a wide range of acceptor substrate specificities. It transferred N-acetylneuraminic acid (NeuAc) to various monosaccharides and various oligosaccharides, and both N-linked and O-linked asialo-glycoprotein. These results suggest that the enzyme can be used as a powerful tool for the study for glycotechnology. 相似文献