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81.
Murakami H Nagashima H Takahagi Y Miyagawa S Fujimura T Toyomura K Nakai R Yamada M Kurihara T Shigehisa T Okabe M Seya T Shirakura R Kinoshita T 《Molecular reproduction and development》2002,61(3):302-311
Porcine membrane cofactor protein (pMCP) is abundantly expressed throughout the body with particularly strong expression on the vascular endothelia. Previous studies demonstrated that the promoter of the pMCP gene induced efficient expression of a human complement regulatory protein, decay-accelerating factor (DAF; CD55), in transgenic mice. In the present study, we tried to produce transgenic pigs with two hybrid genes, 0.9/hDAF and 5.4/hDAF, which were composed of human DAF (hDAF) gene regulated under pMCP promoters of different lengths (0.9 and 5.4 kb). Five live founder transgenic pigs were obtained only with the 0.9/hDAF construct. Although, four founder pigs transmitted the transgene to the second generation, the transmission rates varied among founders. We examined the expression of hDAF in tissues of descendants of two lines (Dm1 and Dm4). Human DAF specific RNAs were confirmed by an RT-PCR analysis in all organs examined. Levels of hDAF protein in the organs from the descendants of Dm1 line were higher than those in the corresponding human organs as determined by enzyme-linked immunosorbent assay. Immunohistochemical studies showed that the tissue distribution of hDAF in the descendants of both lines was similar to that of endogenous pMCP. The expression level of hDAF on the vascular endothelial cells in Dm1 line was twice that on the corresponding human cells. We tested whether proinflammatory cytokines upregulate an efficiency of pMCP promoter on hDAF expression in transgenic pigs. Although the expression of hDAF on the human endothelial cells increased with a combination of cytokines, tumor necrosis factor alpha and interferon-gamma, no cytokine-induced upregulation was seen in the cells of transgenic pigs. The endothelial cells from transgenic pigs exhibited high resistance to the human serum-mediated cytolysis. 相似文献
82.
Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors 总被引:8,自引:0,他引:8
Masuda Y Takatsu Y Terao Y Kumano S Ishibashi Y Suenaga M Abe M Fukusumi S Watanabe T Shintani Y Yamada T Hinuma S Inatomi N Ohtaki T Onda H Fujino M 《Biochemical and biophysical research communications》2002,293(1):396-402
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF, identical to prokineticin 1) is a novel peptide recently identified as a selective mitogen for endocrine gland endothelial cells. The present study demonstrates that EG-VEGF/prokineticin 1 and a peptide closely related to EG-VEGF, prokineticin 2, are cognate ligands of two orphan G-protein-coupled receptors designated ZAQ (=EG-VEGF/PK-R1) and I5E (=EG-VEGF/PK-R2). EG-VEGF/prokineticin 1 and prokineticin 2 induced a transient increase in intracellular calcium ion concentration ([Ca(2+)](i)) with nanomolar potency in Chinese hamster ovary (CHO) cells expressing EG-VEGF/PK-R1 and -R2 and bind to these cells with high affinity and with different receptor selectivity. EG-VEGF/prokineticins provoke rapid phosphorylation of p44/42 MAP kinase and DNA synthesis in the bovine adrenal capillary endothelial cells (BACE). The mRNAs of both EG-VEGF/PK-R1 and -R2 were expressed in BACE. The identification of the receptors for EG-VEGF/prokineticins may provide a novel molecular basis for the regulation of angiogenesis in endocrine glands. 相似文献
83.
The obesity in bilateral ovariectomized rats is related to a decrease in the expression of leptin receptors in the brain. 总被引:4,自引:0,他引:4
Mitsuhiro Kimura Minoru Irahara Toshiyuki Yasui Seiichiro Saito Michiko Tezuka Shuji Yamano Masaharu Kamada Toshihiro Aono 《Biochemical and biophysical research communications》2002,290(4):1349-1353
We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight. 相似文献
84.
85.
Suppression of anoikis by v-Src but not by activated c-H-ras in human gallbladder epithelial cells 总被引:5,自引:0,他引:5
Hisano C Tanaka R Fujishima H Ariyama H Tsuchiya T Tatsumoto T Mitsugi K Nakamura M Nakano S 《Cell biology international》2003,27(5):415-421
Detachment of anchorage-dependent normal epithelial cells from their substratum causes the type of apoptosis known as anoikis, whereas malignant cells can proliferate independently of anchorage. Because src and ras oncogenes are activated in many human cancers, we investigated their role and downstream signaling pathways in anoikis resistance, using HAG-1 human epithelial cells transfected with v-src or activated H-ras. Consequently, anchorage-dependent mock- or ras-transfected cells underwent anoikis. In contrast, anchorage-independent v-Src-transformed cells did not exhibit such apoptotic features. Focal adhesion kinase (FAK), a transducer of integrin, was only activated in v-Src-transformed cells. Herbimycin A, an Src kinase inhibitor, reduced tyrosyl phosphorylation of FAK and reversed resistance to anoikis. However, both protein kinase C (PKC) and phophatidylinositol-3 (PI-3) kinase inhibitors failed to induce anoikis. These data suggest that the ability of activated Src to prevent anoikis may be mediated by Src to a downstream signaling pathway involving FAK, but not Ras, PI-3 kinase, or PKC. 相似文献
86.
Effects of endurance training on three superoxide dismutase isoenzymes in human plasma 总被引:3,自引:0,他引:3
Ookawara T Haga S Ha S Oh-Ishi S Toshinai K Kizaki T Ji LL Suzuki K Ohno H 《Free radical research》2003,37(7):713-719
The effects of endurance training and acute exhaustive exercise on plasma levels of three superoxidedismutase (SOD) isoenzymes and the ability of superoxide generation in neutrophils were studied. Eighteen healthy male students, aged 17-22 years, who volunteered for this study, underwent three months of endurance training in swimming or running. Before and after the training course, they performed acute exercise and blood samples were collected before and after this exercise. The endurance training significantly increased maximal oxygen uptake (VO2max) in all subjects. Neither the endurance training nor the acute exercise affected the plasma CuZn-SOD level. Acute exercise after the training, but not before the training, increased both the plasma Mn-SOD and extracellular SOD (EC-SOD) levels by 33.6 and 33.5%, respectively. The training decreased the EC-SOD level at rest by 22.2%. Acute exercise after the training, but not before the training, increased the plasma lipid peroxide level, suggesting higher oxidative stress in trained subjects during exhaustive exercise. The ability of neutrophils to generate superoxide was increased by the acute exercise, but induction of the superoxide was suppressed after training. These results indicate that EC-SOD levels were changed in a different manner from the CuZn-SOD and Mn-SOD: it was decreased by training but was increased by acute exercise, suggesting that endurance training increases the reserve of EC-SOD in tissues. The results also suggest the possibility of plasma EC-SOD assay as a new index of endurance training. 相似文献
87.
Mori S Shinohata R Renbutsu M Takahashi HK Fang YI Yamaoka K Okamoto M Yamamoto I Nishibori M 《Cell and tissue research》2003,312(3):353-359
Vascular smooth muscle cell (SMC) hyperplasia is known to be an important component in the pathogenesis of arteriosclerosis and restenosis. Although heparin has been well recognized as the representative molecule suppressing SMC growth in vitro, attempts to use heparin as a therapeutic anti-restenosis drug have not favorably influenced the angiographic or clinical outcome after angioplasty in some clinical trials. In this study, we have examined the effect of histidine-rich glycoprotein (HRG), a relatively abundant serum glycoprotein (~100 micrograms/ml in human serum), on the growth inhibition of cultured vascular SMC by heparin. Vascular SMC growth was significantly inhibited by heparin, giving nearly 85% inhibition with 100 micrograms/ml heparin. HRG reversed heparin-induced SMC growth inhibition in a dose dependent manner; 75% restoration of cell growth was observed when 100 micrograms/ml of HRG was co-added with 100 micrograms/ml heparin. Interestingly, micromolar concentrations of the zinc ion (0-10 microM), compatible with concentrations released from activated platelets, were found to enhance the restorative action of HRG. Western blot experiment demonstrated no significant amounts of the HRG moiety in fetal bovine serum, eliminating the possible contribution of contaminant HRG from culture media. These findings indicate that HRG, in combination with the zinc ion, plays a role in modulating the SMC growth response in pathophysiological states and explain the lack of success of heparin as a therapeutic anti-restenosis drug in clinical trials. 相似文献
88.
Shigematsu S Ishida S Hara M Takahashi N Yoshimatsu H Sakata T Korthuis RJ 《Free radical biology & medicine》2003,34(7):810-817
Moderate consumption of red wine has been shown to exert cardioprotection against ischemia/reperfusion. Because oxidant-dependent leukocyte infiltration plays a critical role in ischemia/reperfusion-induced tissue injury, we hypothesized that resveratrol, a red wine constituent polyphenol would attenuate postischemic leukocyte recruitment and subsequent endothelial dysfunction. Intravital microscopic approaches were used to quantify leukocyte/endothelial cell interactions and venular protein leakage in rat mesenteries exposed to either 20 min ischemia and 60 min reperfusion (I/R), oxidants generated by the reaction of hypoxanthine and xanthine oxidase (HX/XO), platelet-activating factor (PAF), or leukotriene B4 (LTB4). I/R or HX/HX produced marked increases in the number of adherent (LA) and emigrated (LE) leukocytes, which were associated with significant increases in venular albumin leakage (VAL). Intravenous administration of resveratrol or superoxide dismutase (SOD) attenuated these increases in LA, LE, and VAL. Superfusion of the mesentery with PAF or LTB4 also markedly increased LA, LE, and VAL. While resveratrol attenuated the proinflammatory effects of PAF, LTB4-induced changes were not affected by resveratrol. Resveratrol prevents leukocyte recruitment and endothelial barrier disruption induced by a number of superoxide-dependent proinflammatory stimuli, including I/R, HX/XO, or PAF. These salutary effects appear to be related to the antioxidant properties of resveratrol and contribute to the cardioprotective actions associated with consumption of red wine. 相似文献
89.
Yamada S Suenaga H Doi K Yoshino S Ogata S 《Bioscience, biotechnology, and biochemistry》2003,67(4):797-802
Spontaneously developing pocks (S pocks) of Streptomyces azureus ATCC14921 were formed by the both functions of conjugative plasmid pSA1 and lysogenic phage SAt2. The formation was affected by the dose of UV irradiation. The mean pock diameter in cultures treated with UV light at 0, 7.1, 14.2 and 21.3 x 10(2) microW. erg/cm, respectively, were 1.3, 0.4, 2.2, and 0.5 mm. The dose affected conjugative plasmid pSA1 related to pock formation. There was UV damage of autonomous pSA1 replicon and UV induction of the chromosomal integrated sequence. Increases and decreases in the amount of autonomous pSA1 replicon corresponded to increases and decreases, respectively, in the diameter of the pocks. Both pSA1 and SAt2 syntheses were developed in the large pocks (1.3 and 2.2 mm), but only SAt2 synthesis was developed in the pinhole pocks (0.4 and 0.5 mm). 相似文献
90.