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101.
Sato Y Suzuki H Sato T Suda T Yoda T Iwakura Y Chida D 《Biochemical and biophysical research communications》2010,403(3-4):253-257
Glucocorticoids are extensively used in anti-inflammatory therapy and are thought to contribute to the steady-state regulation of hematopoiesis and lymphopoiesis. We have previously established MC2R(-/-) mice, a model of familial glucocorticoid deficiency, that show several similarities to patients with this disease, including undetectable levels of corticosterone, despite high levels of ACTH and unresponsiveness to ACTH. In this study, we analyzed the possible roles of endogenous glucocorticoids in hematopoiesis and lymphopoiesis in MC2R(-/-) and CRH(-/-) mice as models of chronic adrenal insufficiency. Our analysis of total peripheral blood cell counts revealed that the number of lymphocytes was increased and the number of erythrocytes was slightly, but significantly, decreased in MC2R(-/-) mice. Numbers of immature double negative (CD4(-) CD8(-)) thymocytes, transitional type 1 B cells in the spleen, and pre-B cells in the bone marrow, were significantly increased in MC2R(-/-) mice, suggesting that endogenous glucocorticoids contribute to steady-state regulation of lymphopoiesis. Oral glucocorticoid supplementation reversed peripheral blood cell counts and reduced numbers of T and B cells in the thymus and the spleen. T cells in the thymus and B cells in the spleen were also increased in CRH(-/-) mice, another animal model of chronic adrenal insufficiency. MC2R(-/-) mice were sensitive to age-related thymic involution, but they were resistant to fasting-associated thymic involution. Our data support the idea that endogenous glucocorticoids contribute to stress-induced as well as steady-state regulation of hematopoiesis and lymphopoiesis. 相似文献
102.
Xiaofeng Wu Akinori Akaike Hachiro Sugimoto 《Biochemical and biophysical research communications》2010,393(3):514-518
Reduction in or dysfunction of glutamate transporter 1 (GLT1) is linked to several neuronal disorders such as stroke, Alzheimer’s disease, and amyotrophic lateral sclerosis. However, the detailed mechanism underlying GLT1 regulation has not been fully elucidated. In the present study, we first demonstrated the effects of mammalian target of rapamycin (mTOR) signaling on GLT1 regulation. We prepared astrocytes cultured in astrocyte-defined medium (ADM), which contains several growth factors including epidermal growth factor (EGF) and insulin. The levels of phosphorylated Akt (Ser473) and mTOR (Ser2448) increased, and GLT1 levels were increased in ADM-cultured astrocytes. Treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor or an Akt inhibitor suppressed the phosphorylation of Akt (Ser473) and mTOR (Ser2448) as well as decreased ADM-induced GLT1 upregulation. Treatment with the mTOR inhibitor rapamycin decreased GLT1 protein and mRNA levels. In contrast, rapamycin did not affect Akt (Ser473) phosphorylation. Our results suggest that mTOR is a downstream target of the PI3K/Akt pathway regulating GLT1 expression. 相似文献
103.
Okuno M Minami K Okumachi A Miyawaki K Yokoi N Toyokuni S Seino S 《American journal of physiology. Endocrinology and metabolism》2007,292(1):E158-E165
We recently found that pancreatic acinar cells isolated from normal adult mouse can transdifferentiate into insulin-secreting cells in vitro. Using two different animal models of type 1 diabetes, we show here that insulin-secreting cells can also be generated from pancreatic acinar cells of rodents in the diabetic state with absolute insulin deficiency. When pancreatic acinar cells of streptozotocin-treated mice were cultured in suspension in the presence of epidermal growth factor and nicotinamide under low-serum condition, expressions of insulin genes gradually increased. In addition, expressions of other pancreatic hormones, including glucagon, somatostatin, and pancreatic polypeptide, were also induced. Analysis by the Cre/loxP-based direct cell lineage tracing system revealed that these newly made cells originated from amylase-expressing pancreatic acinar cells. Insulin secretion from the newly made cells was significantly stimulated by high glucose and other secretagogues. In addition, insulin-secreting cells were generated from pancreatic acinar cells of Komeda diabetes-prone rats, another animal model of type 1 diabetes. The present study demonstrates that insulin-secreting cells can be generated by transdifferentiation from pancreatic acinar cells of rodents in the diabetic state and further suggests that pancreatic acinar cells represent a potential source of autologous transplantable insulin-secreting cells for treatment of type 1 diabetes. 相似文献
104.
Nishimura K Segawa H Goto T Morishita M Masago A Takahashi H Ohmiya Y Sakaguchi T Asada M Imamura T Shimotono K Takayama K Yoshida T Nakanishi M 《The Journal of biological chemistry》2007,282(37):27383-27391
Persistent and stable expression of foreign genes has been achieved in mammalian cells by integrating the genes into the host chromosomes. However, this approach has several shortcomings in practical applications. For example, large scale production of protein pharmaceutics frequently requires laborious amplification of the inserted genes to optimize the gene expression. The random chromosomal insertion of exogenous DNA also results occasionally in malignant transformation of normal tissue cells, raising safety concerns in medical applications. Here we report a novel cytoplasmic RNA replicon capable of expressing installed genes stably without chromosome insertion. This system is based on the RNA genome of a noncytopathic variant Sendai virus strain, Cl.151. We found that this variant virus establishes stable symbiosis with host cells by escaping from retinoic acid-inducible gene I-interferon regulatory factor 3-mediated antiviral machinery. Using a cloned genome cDNA of Sendai virus Cl.151, we developed a recombinant RNA installed with exogenous marker genes that was maintained stably in the cytoplasm as a high copy replicon (about 4 x 10(4) copies/cell) without interfering with normal cellular function. Strong expression of the marker genes persisted for more than 6 months in various types of cultured cells and for at least two months in rat colonic mucosa without any apparent side effects. This stable RNA replicon is a potentially valuable genetic platform for various biological applications. 相似文献
105.
Chen Z Takahashi M Naruse T Nakajima T Chen YW Inoue Y Ishikawa I Iwai T Kimura A 《Human genetics》2007,122(3-4):367-372
Buerger disease (BD) is an occulusive vascular disease of unknown etiology. Although cigarette smoking is a well-known risk
factor of BD, genetic factors may also play a role in the etiology. Because chronic bacterial infection such as oral periodontitis
is suggested to be involved in the pathogenesis of BD, gene polymorphisms involved in the infectious immunity might be associated
with BD as the genetic factor(s). We have previously reported that HLA-DRB1*1501 and B54 was associated with BD in Japanese.
In this study, polymorphisms in HLA-DPB1, DRB1 and B were analyzed in 131 Japanese BD patients and 227 healthy controls. In
addition, we investigated a functional promoter polymorphism, −260 C > T, of CD14 that is a main receptor of bacterial lipopolysaccharide.
It was found that the frequencies of CD14 TT genotype [37.4 vs. 24.2%, P = 0.008 OR = 1.87, 95% confidence interval (CI); 1.18, 2.97], DRB1*1501 (34.4 vs. 13.2%, P
c = 4.4 × 10−5, OR = 3.44, 95%CI; 2.06, 5.73) and DPB1*0501 (79.4 vs. 55.1%, P
c = 4.7 × 10−5, OR = 3.14, 95%CI; 1.93, 5.11) were significantly higher in the patients than in the controls, demonstrating that at least
three genetic markers were associated with BD. Stratification analyses of these associated markers suggested synergistic roles
of the genetic factors. Odds ratios ranged from 4.72 to 12.57 in individuals carrying any two of these three markers. These
findings suggested that the susceptibility to BD was in part controlled by genes involved in the innate and adaptive immunity. 相似文献
106.
Terauchi T Asai N Doko T Taguchi R Takenaka O Sakurai H Yonaga M Kimura T Kajiwara A Niidome T Kume T Akaike A Sugimoto H 《Bioorganic & medicinal chemistry》2007,15(22):7098-7107
We present efficient syntheses of serofendic acids A and B (SA-A and SA-B), novel neuroprotective substances isolated from fetal calf serum. Biological and pharmacological evaluation showed that SA-A and SA-B have potent protective action against glutamate-induced neurotoxicity, but do not interact directly with glutamate receptors. A pharmacokinetic study showed that they have good oral bioavailability in rats. The results indicate that SA-A and SA-B are potential lead compounds for candidate drugs to treat various neurological disorders. 相似文献
107.
Kawaguchi A Asano H Matsushima K Wada T Yoshida S Ichida S 《Neurochemical research》2007,32(9):1469-1475
It is well known that morphological and functional changes during neural differentiation sometimes accompany the expression
of various voltage-gated ion channels. In this work, we investigated whether the enhancement of sodium current in differentiated
neuroblastoma × glioma NG108-15 cells treated with dibutyryl cAMP is related to the expression of voltage-gated sodium channels.
The results were as follows. (1) Sodium current density on peak voltage in differentiated cells was significantly enhanced
compared with that in undifferentiated cells, as detected by the whole-cell patch clamp method. The steady-state inactivation
curve in differentiated cells was similar to that for undifferentiated cells, but a hyperpolarized shift in the activation
curve for differentiated cells was observed. The sodium currents of differentiated and undifferentiated cells were completely
inhibited by 10−7 M tetrodotoxin (TTX). (2) The only NaV mRNA with an increased expression level during neuronal differentiation was that for NaV1.7, as observed by real-time PCR analysis. (3) The increase in the level of NaV1.7 α subunit expression during neuronal differentiation was also observed by immunocytochemistry; in particular, the localization
of NaV1.7 α subunits on the soma, varicosities and growth cone was significant. These results suggest that the enhancement of TTX-sensitive
sodium current density in differentiated NG108-15 cells is mainly due to the increase in the expression of the TTX-sensitive
voltage-gated Na+ channel, NaV1.7. 相似文献
108.
Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres 总被引:4,自引:0,他引:4
Alonso A Fritz B Hasson D Abrusan G Cheung F Yoda K Radlwimmer B Ladurner AG Warburton PE 《Genome biology》2007,8(7):R148
Background
Mammalian centromere formation is dependent on chromatin that contains centromere protein (CENP)-A, which is the centromere-specific histone H3 variant. Human neocentromeres have acquired CENP-A chromatin epigenetically in ectopic chromosomal locations on low-copy complex DNA. Neocentromeres permit detailed investigation of centromeric chromatin organization that is not possible in the highly repetitive alpha satellite DNA present at endogenous centromeres. 相似文献109.
110.