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81.
82.
Statins, specific inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, are now widely used for treatment of patients with hypercholesterolemia. In addition to the reduction of cholesterol biosynthesis, accumulating evidence indicates that statins have several pleiotropic effects especially on cardiovascular system. However, the exact role of statin in cardiac myocytes remains unclear. In the present study, we investigated whether atorvastatin induces vascular endothelial growth factor (VEGF) release in cardiac myocytes, and the underlying mechanism. We observed that atorvastatin significantly stimulated VEGF release in a dose-dependent manner. It induced the phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase but not SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase). The atorvastatin-induced VEGF release was enhanced by PD98059, which is a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase (MEK). Further, it was significantly reduced by SB203580, a specific inhibitor of p38 MAP kinase. Furthermore, the atorvastatin-induced phosphorylation of p38 MAP kinase was attenuated by SB203580, whereas it was enhanced by PD98059. Taken together, these results suggest that the atorvastatin-induced VEGF release in cardiac myocytes is positively regulated by p38 MAP kinase and negatively regulated byp44/p42 MAP kinase and that the atorvastatin-induced phosphorylation of p38 MAP kinase is regulated by p44/p42 MAP kinase in these cells. 相似文献
83.
84.
The interaction between single-stranded RNAs and liposomes was studied using UV, Fourier Transform Infrared spectroscopy (FTIR) and Circular Dichroism spectroscopy (CD). The effect of the surface characteristics of liposomes, which were composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and modified with cholesterol (Ch) or 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), on the liposome–RNA interaction was investigated. The fluorescence of 6-(p-toluidino)naphthalene-2-sulfonate (TNS) embedded in the liposome surface (ε = 30–40) was decreased in the presence of tRNA, suggesting that single-stranded tRNA could bind onto the liposome. The dehydration of –PO2− –, guanine (G) and cytosine (C) of tRNA molecules in the presence of liposomes suggested both an electrostatic interaction (phosphate backbone of tRNA and trimethylammonium group of POPC, DOTAP) and a hydrophobic interaction (guanine or cytosine of tRNA and aliphatic tail of lipid). The tRNA conformation on the liposome was determined by CD spectroscopy. POPC/Ch (70/30) maintained tRNA conformation without any denaturation, while POPC/DOTAP(70/30) drastically denatured it. The mRNA translation was evaluated in an Escherichia coli cell-free translation system. POPC/Ch(70/30) enhanced expression of green fluorescent protein (GFP) (116%) while POPC/DOTAP(70/30) inhibited (37%), suggesting that the conformation of RNAs was closely related to the translation efficiency. Therefore, single-stranded RNAs could bind to liposomal membranes through electrostatic and hydrophobic attraction, after which conformational changes were induced depending on the liposome characteristics. 相似文献
85.
Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11 in myelosuppressed mice 总被引:9,自引:0,他引:9
Recombinant human interleukin 11 (rhIL-11) has previously been shown to ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1 developed severe thrombocytopenia with a nadir of platelet counts at 24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500 microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration of thrombocytopenia and enhanced the platelet recovery, and also enhanced the recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow megakaryocyte progenitors and megakaryocyte counts preceded the decrease in platelet counts by MMC treatment. RhIL-11 induced an increase in the number of megakaryocyte progenitors from day 4 to 14, followed by an increase in the megakaryocytes by day 20. There was a ploidy shift in megakaryocytes towards lower ploidy cells by day 9 in myelosuppressed mice. RhIL-11 caused a shift towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These results suggest that rhIL-11 ameliorates the thrombocytopenia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells. 相似文献
86.
Retinal Müller glia can serve as a source for regeneration of damaged retinal neurons in fish, birds and mammals. However, the proliferation rate of Müller glia has been reported to be low in the mammalian retina. To overcome this problem, growth factors and morphogens have been studied as potent promoters of Müller glial proliferation, but the molecular mechanisms that limit the proliferation of Müller glia in the mammalian retina remain unknown. In the present study, we found that the degree of damage-induced Müller glia proliferation varies across mouse strains. In mouse line 129×1/SvJ (129), there was a significantly larger proliferative response compared with that observed in C57BL/6 (B6) after photoreceptor cell death. Treatment with a Glycogen synthase kinase 3 (GSK3) inhibitor enhanced the proliferation of Müller glia in 129 but not in B6 mouse retinas. We therefore focused on the different gene expression patterns during retinal degeneration between B6 and 129. Expression levels of Cyclin D1 and Nestin correlated with the degree of Müller glial proliferation. A comparison of genome-wide gene expression between B6 and 129 showed that distinct sets of genes were upregulated in the retinas after damage, including immune response genes and chromatin remodeling factors. 相似文献
87.
88.
Hiroshi Tamura Noriko Wada Hong Zhang Hironari Unrin Takafumi Watanabe Tetsuya Suga 《Cell biochemistry and biophysics》2000,32(1-3):325-327
Peroxisome proliferators (PPs) are nongenotoxic compounds causing the emergence of hepatocellular carcinoma in rodents, but
the mechanisms of the hepatocarcinogenesis have been unclear. The authors examined the changes in phosphorylation of nuclear
proteins after treatment with (4-chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643). Wy-14,643 (0.1% w/w in
diet) was given orally to male F-344 rats for up to 80 wk. In the hepatocarcinomas induced by Wy-14,643, phosphorylation of
13 kDa nuclear protein (NP 13), which was resistant to alkaline treatment, was significantly increased. NP 13 phosphorylation
gradually increased, dependent on treatment period. Furthermore, in the hepatocarcinomas induced by other PP, di(2-ethylhexyl)phthalate,
increase in NP13-phospholyration was also observed. Therefore, NP 13-phospholyration may relate to development of preneoplastic
or neoplastic lesions induced by PPs. 相似文献
89.
H. Suzuki M. Kishimoto Y. Kamoshita T. Omasa Y. Katakura Kenn-ichi Suga 《Bioprocess and biosystems engineering》2000,22(5):433-440
On line control coupled with an expert system was constructed for the control of a fed-batch culture with the aim of achieving a high cell density. During the cultivation, the expert system could monitor the extents of sufficiencies in the amounts of chemical elements in the medium every 10 min, and suggest a modification to the feeding control policy if the amount of a particular component was inadequate for cell growth. However, we often encounter such a kind of cultivations in which some particular carbon source such as glucose and ethanol should be controlled at low concentration in many culture processes, because the excess feeding might cause the growth inhibition by its own accumulation in the culture broth, or the biproduct accumulation like as lactate or acetate, unsuitable substances for smoothed growth. In this study, we developed an online control system based on production rules which managed the glucose feed rate from DO signal. The online control was carried out by the control computer connected with the other computer for expert system, because a relatively long time (several minutes) was needed for the inference of the expert system and the influence of the starvation of carbon source on the cell growth is not negligible even in several minutes. The on-line control system with expert system was applied to the production of cell mass of E. coli W3110 and the final cell concentration reached 137 g-dry cell weight/l. 相似文献
90.
T Akaike S Fujii A Kato J Yoshitake Y Miyamoto T Sawa S Okamoto M Suga M Asakawa Y Nagai H Maeda 《FASEB journal》2000,14(10):1447-1454
Nitric oxide (NO), superoxide (O(2)(-)), and their reaction product peroxynitrite (ONOO(-)) are generated in excess during a host's response against viral infection, and contribute to viral pathogenesis by promoting oxidative stress and tissue injury. Here we demonstrate that NO and peroxynitrite greatly accelerates the mutation of Sendai virus (SeV), a nonsegmented negative-strand RNA virus, by using green fluorescent protein (GFP) inserted into and expressed by a recombinant SeV (GFP-SeV) as an indicator for mutation. GFP-SeV mutation frequencies were much higher in the wild-type mice than in those lacking inducible NO synthase, suggesting that mutation of the virus in vivo is NO dependent. High levels of NO and NO-mediated oxidative stress were induced by GFP-SeV infection in the lung of the wild-type mice, but not in the iNOS-deficient mice, as evidenced by electron spin resonance spectroscopy and immunohistochemical analysis for nitrotyrosine formation as well as histopathological examination. Furthermore, peroxynitrite, an NO-derived reactive nitrogen intermediate, enhanced viral mutation in vitro. These results indicate that the oxidative stress induced by NO produced during the natural course of viral infection increases mutation, expands the quasispecies spectrum, and facilitates evolution of RNA viruses. 相似文献