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111.
Oda M Shiihara R Ohmae Y Kabura M Takagishi T Kobayashi K Nagahama M Inoue M Abe T Setsu K Sakurai J 《Biochimica et biophysica acta》2012,1822(10):1581-1589
A characteristic feature of gas gangrene with Clostridium perfringens (C. perfringens) is the absence of neutrophils within the infected area and the massive accumulation of neutrophils at the vascular endothelium around the margins of the necrotic region. Intravenous injection of C. perfringens alpha-toxin into mice resulted in the accumulation of neutrophils at the vascular endothelium in lung and liver, and release of GRO/KC, a member of the CXC chemokine family with homology to human interleukin-8 (IL-8). Alpha-toxin triggered activation of signal transduction pathways causing mRNA expression and production of IL-8, which activates migration and binding of neutrophils, in A549 cells. K252a, a tyrosine kinase A (TrkA) inhibitor, and siRNA for TrkA inhibited the toxin-induced phosphorylation of TrkA and production of IL-8. In addition, K252a inhibited the toxin-induced phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). PD98059, an ERK1/2 inhibitor, depressed phosphorylation of ERK1/2 and nuclear translocation of nuclear factor kappa B (NF-κB) p65, but SB203580, a p38 MAPK inhibitor, did not. On the other hand, PD98059 and SB203580 suppressed the toxin-induced production of IL-8. Treatment of the cells with PD98059 resulted in inhibition of IL-8 mRNA expression induced by the toxin and that with SB203580 led to a decrease in the stabilization of IL-8 mRNA. These results suggest that alpha-toxin induces production of IL-8 through the activation of two separate pathways, the ERK1/2/NF-κB and p38 MAPK pathways. 相似文献
112.
Yamashita T Nagano K Kanasaki S Maeda Y Furuya T Inoue M Nabeshi H Yoshikawa T Yoshioka Y Itoh N Abe Y Kamada H Tsutsumi Y Tsunoda S 《Biochemical and biophysical research communications》2012,421(1):140-144
Mesothelioma is a highly malignant tumor with a poor prognosis and limited treatment options. Although cisplatin (CDDP) is an effective anticancer drug, its response rate is only 20%. Therefore, discovery of biomarkers is desirable to distinguish the CDDP-susceptible versus resistant cases. To this end, differential proteome analysis was performed to distinguish between mesothelioma cells of different CDDP susceptibilities, and this revealed that expression of annexin A4 (ANXA4) protein was higher in CDDP-resistant cells than in CDDP-susceptible cells. Furthermore, ANXA4 expression levels were higher in human clinical malignant mesothelioma tissues than in benign mesothelioma and normal mesothelial tissues. Finally, increased susceptibility was observed following gene knockdown of ANXA4 in mesothelioma cells, whereas the opposite effect was observed following transfection of an ANXA4 plasmid. These results suggest that ANXA4 has a regulatory function related to the cisplatin susceptibility of mesothelioma cells and that it could be a biomarker for CDDP susceptibility in pathological diagnoses. 相似文献
113.
Saito M Kato Y Ito E Fujimoto J Ishikawa K Doi A Kumazawa K Matsui A Takebe S Ishida T Azuma S Mochizuki H Kawamura Y Yanagisawa Y Honma R Imai J Ohbayashi H Goshima N Semba K Watanabe S 《FEBS letters》2012,586(12):1708-1714
Gene amplification is a major genetic alteration in human cancers. Amplicons, amplified genomic regions, are believed to contain "driver" genes responsible for tumorigenesis. However, the significance of co-amplified genes has not been extensively studied. We have established an integrated analysis system of amplicons using retrovirus-mediated gene transfer coupled with a human full-length cDNA set. Applying this system to 17q12-21 amplicon observed in breast cancer, we identified GRB7 as a context-dependent oncogene, which modulates the ERBB2 signaling pathway through enhanced phosphorylation of ERBB2 and Akt. Our work provides an insight into the biological significance of gene amplification in human cancers. 相似文献
114.
Chihara T Hashimoto M Osman A Hiyoshi-Yoshidomi Y Suzu I Chutiwitoonchai N Hiyoshi M Okada S Suzu S 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(8):3620-3627
HIV-1 proteins, including Tat, gp120, and Nef, activate macrophages (MΦ), which is consistent with the fact that HIV-1 infection is characterized by sustained immune activation. Meanwhile, MΦ are functionally classified into two types: proinflammatory M1-MΦ and anti-inflammatory M2-MΦ. We show that HIV-1 proteins, particularly Nef, preferentially activate M2-MΦ. Extracellular Tat, gp120, and Nef activated MAPK and NF-κB pathways in human peripheral blood monocyte-derived MΦ. However, the activation was marked in M-CSF-derived M2-MΦ but not GM-CSF-derived M1-MΦ. Nef was the most potent activator, and its signaling activation was comparable to that by TNF-α. Indeed, Nef was internalized more rapidly by M2-MΦ than by M1-MΦ. The myristoylation and proline-rich motif of Nef were responsible for the observed signaling activation. Consistent with the activation of MAPK/NF-κB pathways, Nef stimulated the production of a number of proinflammatory cytokines/chemokines by M2-MΦ. However, Nef reduced the expression of CD163 and phagocytosis, the characteristic markers of M2-MΦ, indicating that Nef drives an M2-like to M1-like phenotypic shift. Because the differentiation of most tissue MΦ depends on M-CSF and its receptor, which is the essential axis for the anti-inflammatory M2-MΦ phenotype, the current study reveals an efficient mechanism by which HIV-1 proteins, such as Nef, induce the proinflammatory MΦ. 相似文献
115.
Keisuke Yaku Yuka Enami Chika Kurajyo Isao Matsui-Yuasa Yotaro Konishi Akiko Kojima-Yuasa 《Molecular and cellular biochemistry》2012,370(1-2):7-14
Dietary fiber fermentation by the colonic bacterial flora produces short-chain fatty acids, acetate, propionate and butyrate. Among them, butyrate is considered to be the major energy substrate for colonocytes and, at least in rats, seems to protect against colonic carcinogenesis. In this study, we examined the effect and the mechanisms of short-chain fatty acids on the activity of phase 2 enzymes. Sodium butyrate increased phase 2 enzyme activities in normal rat small intestine epithelial cells, Glutathione S-transferase and NAD(P)H:quinone oxidoreductase (NQO) in a dose-dependent manner; however, other short-chain fatty acids did not increase them. The mechanism of the induction of phase 2 enzymes with sodium butyrate sodium butyrate, but not other short-chain fatty acids was related to the increase of NF-E2-related factor 2 (Nrf2) nuclear translocation and the decrease in the levels of nuclear fraction p53. Sodium butyrate also caused enhancement of Nrf2 mRNA levels and suppression of p53 mRNA levels. Sodium butyrate enhances the activities of phase 2 enzymes via an increase in the Nrf2 protein levels in the nucleus and a decrease in the mRNA and protein levels of p53. 相似文献
116.
Branched-chain amino acid-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride 总被引:1,自引:0,他引:1
Kengo Ichikawa Takehiro Okabayashi Yasuo Shima Tatsuo Iiyama Yuka Takezaki Masaya Munekage Tsutomu Namikawa Takeki Sugimoto Michiya Kobayashi Toshiki Mimura Kazuhiro Hanazaki 《Molecular biology reports》2012,39(12):10803-10810
Oxidative stress (OS) plays an important role in the progression of chronic liver disease including organ injury and hypoalbuminemia. Long-term oral supplementation with branched-chain amino acids (BCAAs) can inhibit liver dysfunction but their role in the prevention of liver fibrosis and injury to the liver is unclear. The aim of this study was to assess how BCAAs preserve liver function from OS. To investigate how BCAAs specifically prevent OS, we evaluated the effect of oral supplementation with BCAAs on OS using a rat liver cirrhosis model. Liver cirrhosis was induced in ten male Sprague–Dawley rats by administering carbon tetrachloride for 12?weeks. Five of the ten carbon tetrachloride-treated rats were assigned to a control group and five to a BCAA group. BCAA-supplementation significantly preserved plasma albumin concentrations and significantly inhibited the occurrence of organ injury as determined by blood chemistry analysis. Hepatic expression of OGG1 mRNA was increased in the BCAA group compared to the control group. In the BCAA group, increased hepatic levels of OGG1 protein were found by western blot. On the other hand, the number of 8-OHdG-positive cells was significantly higher in liver sections taken 1?month after carbon tetrachloride treatment. Furthermore, OGG1-positive cells were significantly increased in the hepatocytes around the central vein. BCAA was found to reduce OS, which could possibly lead to a decrease in the occurrence of hypoalbuminemia and organ injury. Our results indicate that BCAA-enriched nutrients stimulate antioxidant DNA repair in a rat model of liver injury induced by carbon tetrachloride. 相似文献
117.
Miyazaki T Takenaka T Inoue T Sato M Miyajima Y Nodera M Hanyu M Ohno Y Shibazaki S Suzuki H 《Biological trace element research》2012,145(3):375-381
Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible
nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated
in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in
NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague–Dawley rats (body weight,
100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After
4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional
72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS
immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO
levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in
ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from
basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating
iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group
and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces
overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction
of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced
iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative stresses in the
lung, and these stresses may be involved low immunity of zinc deficiency states. 相似文献
118.
Hara KY Kim S Yoshida H Kiriyama K Kondo T Okai N Ogino C Fukuda H Kondo A 《Applied microbiology and biotechnology》2012,93(4):1495-1502
Glutathione is a valuable tri-peptide that is widely used in the pharmaceutical, food, and cosmetic industries. Glutathione
is produced industrially by fermentation using Saccharomyces cerevisiae, and supplementation of fermentation with several amino acids can increase intracellular GSH content. More recently, however,
focus has been given to protein as a resource for biofuel and fine chemical production. We demonstrate that expression of
a protease on the cell surface of S. cerevisiae enables the direct use of keratin and soy protein as a source of amino acids and that these substrates enhanced intracellular
GSH content. Furthermore, fermentation using soy protein also enhanced cell concentration. GSH fermentation from keratin and
to a greater extent from soy protein using protease-displaying yeast yielded greater GSH productivity compared to GSH fermentation
with amino acid supplementation. This protease-displaying yeast is potentially applicable to a variety of processes for the
bio-production of value-added chemicals from proteinaceous biomass resources. 相似文献
119.
Kawamura K Sakuma A Nakamura Y Oguri T Sato N Kido N 《Microbiology and immunology》2012,56(7):431-440
To develop a novel low-temperature plasma sterilizer using pure N(2) gas as a plasma source, we evaluated bactericidal ability of a prototype apparatus provided by NGK Insulators. After determination of the sterilizing conditions without the cold spots, the D value of the BI of Geobacillus stearothermophilus endospores on the filter paper was determined as 1.9 min. However, the inactivation efficiency of BI carrying the same endospores on SUS varied to some extent, suggesting that the bactericidal effect might vary by materials of sterilized instruments. Staphylococcus aureus and Escherichia coli were also exposed to the N(2) gas plasma and confirmed to be inactivated within 30 min. Through the evaluation of bactericidal efficiency in a sterilization bag, we concluded that the UV photons in the plasma and the high-voltage pulse to generate the gas plasma were not concerned with the bactericidal effect of the N(2) gas plasma. Bactericidal effect might be exhibited by activated nitrogen atoms or molecular radicals. 相似文献
120.
Caffeic acid is a biologically active molecule that has various beneficial properties, including antioxidant, anticancer, and anti-inflammatory activities. In this study, we explored the catalytic potential of a bacterial cytochrome P450, CYP199A2, for the biotechnological production of caffeic acid. When the CYP199A2 enzyme was reacted with p-coumaric acid, it stoichiometrically produced caffeic acid. The crystal structure of CYP199A2 shows that Phe at position 185 is situated directly above, and only 6.35 Å from, the heme iron. This F185 residue was replaced with hydrophobic or hydroxylated amino acids using site-directed mutagenesis to create mutants with novel and improved catalytic properties. In whole-cell assays with the known substrate of CYP199A2, 2-naphthoic acid, only the wild-type enzyme hydroxylated 2-naphthoic acid at the C-7 and C-8 positions, whereas all of the active F185 mutants exhibited a preference for C-5 hydroxylation. Interestingly, several F185 mutants (F185V, F185L, F185I, F185G, and F185A mutants) also acquired the ability to hydroxylate cinnamic acid, which was not hydroxylated by the wild-type enzyme. These results demonstrate that F185 is an important residue that controls the regioselectivity and the substrate specificity of CYP199A2. Furthermore, Escherichia coli cells expressing the F185L mutant exhibited 5.5 times higher hydroxylation activity for p-coumaric acid than those expressing the wild-type enzyme. By using the F185L whole-cell catalyst, the production of caffeic acid reached 15 mM (2.8 g/liter), which is the highest level so far attained in biotechnological production of this compound. 相似文献