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991.
Cohen RI Hassell AM Ye X Marzouk K Liu SF 《Biochemical and biophysical research communications》2003,307(3):451-458
Studies of the regulation of iNOS expression have provided many contradictory results. Comparing iNOS expression profile between cell types or organs of the same animal under the same experimental conditions may provide an explanation for these conflicting results. We have examined iNOS mRNA and protein expression in heart and liver of the same group of pigs. We found that there is a sharp difference in iNOS expression between heart and liver. The iNOS mRNA and protein was constitutively expressed in the heart at high level, but was not detectable in the liver of the same control animal. Lipopolysaccharide (LPS, 100 microg/kg, i.v.) caused a marked iNOS induction in the liver, but significantly down-regulated iNOS expression in the heart. This differential iNOS expression appears to be physiologically relevant, since LPS and the iNOS inhibitor, S-methylisothiourea, exerted different effects on hepatic and myocardial blood flow. Our data demonstrate a fundamental difference in iNOS regulation in the heart and liver of swine, and may explain the contradictory data on the regulation of iNOS expression. 相似文献
992.
993.
994.
Vector-based RNAi,a novel tool for isoform-specific knock-down of VEGF and anti-angiogenesis gene therapy of cancer 总被引:72,自引:0,他引:72
Zhang L Yang N Mohamed-Hadley A Rubin SC Coukos G 《Biochemical and biophysical research communications》2003,303(4):1169-1178
Vascular endothelial growth factor (VEGF) carries out multifaceted functions in tumor development, and it exists as at least five isoforms with distinct biologic activities and clinical implications. Several strategies have been developed to block VEGF for cancer therapy; however, the approach to target-specific VEGF isoform(s) has not been explored to date. In the present study, we show that DNA vector-based RNA interference (RNAi), in which RNAi sequences targeting murine VEGF isoforms are inserted downstream of an RNA polymerase III promoter, has potential applications in isoform-specific "knock-down" of VEGF. Large molecular weight VEGF isoforms were specifically reduced in vitro in the presence of isoform-specific RNAi constructs. Additionally, H1 promoter may be superior to U6 promoter when used for vector-based RNAi of VEGF isoforms. This strategy provides a novel tool to study the function of various VEGF isoforms and may contribute to VEGF isoform-specific treatment in cancer. 相似文献
995.
Adenoviral transfection of hepatocytes with the thioredoxin gene confers protection against apoptosis and necrosis 总被引:3,自引:0,他引:3
Tsutsui T Koide H Fukahori H Isoda K Higashiyama S Maeda I Tashiro F Yamato E Miyazaki J Yodoi J Kawase M Yagi K 《Biochemical and biophysical research communications》2003,307(4):765-770
A recombinant adenovirus vector containing the human thioredoxin (TRX) gene was constructed using the Cre-loxP recombination system and used to transfect rat hepatocytes with very high efficiency. The TRX gene was expressed in a dose-dependent manner and significantly modulated rat cellular functions. The TRX gene conferred resistance to oxidative stress, such as hydrogen peroxide treatment, on the host hepatocytes. FACS analysis of DNA fragmentation showed that the TRX gene suppressed hepatocyte apoptosis. It also significantly extended the life span of hepatocytes cultured conventionally on polystyrene plates. Liver-specific functions were maintained in the viability-modulated hepatocytes. Moreover, TRX expression did not affect hepatocyte spheroid formation and it extensively suppressed necrosis in the internal cells. Thus, the transfection of hepatocytes with the TRX gene successfully confers global maintenance of liver functions. These findings provide important information for the development of bioartificial liver support systems and gene therapy for liver diseases. 相似文献
996.
Prolonged culture in low glucose induces apoptosis of rat pancreatic beta-cells through induction of c-myc 总被引:4,自引:0,他引:4
Van de Casteele M Kefas BA Cai Y Heimberg H Scott DK Henquin JC Pipeleers D Jonas JC 《Biochemical and biophysical research communications》2003,312(4):937-944
Prolonged culture in low-glucose concentrations (=5mM) induces apoptosis in pancreatic beta-cells by a poorly defined mechanism. We now show that, in both purified rat beta-cells and isolated rat islets, culture in the presence of 3 or 5mM (G3-G5) instead of 10mM glucose (G10) induces a large increase in c-myc expression before onset of a caspase-dependent apoptosis. These effects were prevented by addition of leucine and glutamine to G3 and G5, and were mimicked by addition of the mitochondrial poison azide to G10. In contrast, inhibition of Ca(2+) influx and insulin secretion with diazoxide under control conditions did not stimulate islet c-myc expression nor beta-cell apoptosis. In rat beta-cells, adenovirus-mediated c-myc overexpression increased their rate of apoptosis, whereas antisense-c-myc expression reduced low-glucose-induced apoptosis by approximately 50%. In the insulin producing MIN6 cell line, apoptosis induction by either low glucose or an activator of AMP-activated protein kinase (AMPK) was associated with c-myc mRNA and protein upregulation. In conclusion, stimulation of beta-cell apoptosis by prolonged culture at low glucose partly results from early and sustained induction of beta-cell c-myc expression. These effects may be due to sustained restriction in nutrient-derived metabolic signals. 相似文献
997.
Kubosaki A Nishimura-Nasu Y Nishimura T Yusa S Sakudo A Saeki K Matsumoto Y Itohara S Onodera T 《Biochemical and biophysical research communications》2003,307(4):810-813
The purpose of this report was to determine the effect of prion protein (PrP) gene disruption on T lymphocyte function. Previous studies have suggested that normal cellular prion protein (PrP(c)) binds to copper and Cu(2+) is essential for interleukin-2 (IL-2) mRNA synthesis. In this study, IL-2 mRNA levels in a copper-deficient condition were investigated using T lymphocytes from prion protein gene-deficient (PrP(0/0)) and wild-type mice. Results showed that Cu(2+) deficiency had no effect on PrP(c) expression in Con A-activated splenocytes. However, a delay in IL-2 gene expression was observed in PrP(0/0) mouse T lymphocyte cultures using Con A and Cu(2+)-chelator. These results suggest that PrP(c) expression may play an important role in rapid Cu(2+) transfer in T lymphocytes. The rapid transfer of Cu(2+) in murine T lymphocytes could be one of the normal functions of PrP(c). 相似文献
998.
DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues 总被引:5,自引:0,他引:5
Wang PL Ohura K Fujii T Oido-Mori M Kowashi Y Kikuchi M Suetsugu Y Tanaka J 《Biochemical and biophysical research communications》2003,305(4):970-973
In the inflammatory gingival tissues of patients with periodontitis, cytokines such as interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha have been detected. Gingival fibroblasts are the major constituents of gingival tissue. We recently demonstrated that lipopolysaccharide (LPS) from periodontopathic bacteria induces inflammatory reactions in various tissues via CD14 and/or Toll-like receptors (TLRs) in gingival tissues [Biochem. Biophys. Res. Commun. 273 (2000) 1161]. To confirm this, we examined the expression of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, CD14, TLR2, and TLR4 in human gingival fibroblasts (HGFs) obtained from patients with healthy or inflammatory gingiva using DNA microarray analysis. We also studied the expression levels of these proteins by flow cytometric analysis (FACS). The expression levels of all eight genes in the HGFs of the Inflammatory group were significantly higher than those in the Healthy group on DNA microarray analysis. FACS revealed that the expression levels of all eight proteins on the HGFs of the Inflammatory group were higher than those on the Healthy group. Our data indicated that these eight proteins in HGFs are involved in inflammatory conditions in the gingiva, including periodontal disease. Our results suggested that these eight proteins, in turn, act directly or indirectly on the immune response by activating host cells involved in inflammatory processes. 相似文献
999.
Design considerations for efficient and effective microarray studies 总被引:11,自引:0,他引:11
Kerr MK 《Biometrics》2003,59(4):822-828
This article describes the theoretical and practical issues in experimental design for gene expression microarrays. Specifically, this article 1) discusses the basic principles of design (randomization, replication, and blocking) as they pertain to microarrays, and 2) provides some general guidelines for statisticians designing microarray studies. 相似文献
1000.