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51.
Leptin plays an important role in the central regulation of body weight and arterial pressure via activation of leptin receptors (Ob-Rs) in the hypothalamic area, including the hypothalamic paraventricular nucleus (PVN). The present study was undertaken to investigate whether endogenous leptin in the PVN plays a dual role in the tonic regulation of body weight and arterial pressure. Adult, male normal-weight Sprague-Dawley rats, which were anesthetized and maintained with propofol, were used. A direct bilateral microinjection into the PVN of an antisense oligonucleotide against Ob-R mRNA (ASON1, 50 pmol) significantly increased the daily food intake and body weight gain, effects which lasted for at least 14 days. The same treatment, on the other hand, had no appreciable effect on the basal mean systemic arterial pressure (SAP), heart rate (HR), or power density of the vasomotor components of SAP signals, the experimental index of neurogenic sympathetic vasomotor tone. ASON1 treatment also exerted an insignificant effect on the baroreceptor reflex control of HR. Western blot analysis revealed that a bilateral microinjection into the PVN of ASON1 (50 pmol) significantly decreased the expression of the Ob-R protein in the hypothalamus. The same treatment also attenuated hypertension, tachycardia, and the increase in the power density of the vasomotor components of the SAP signals induced by exogenous bilateral application of leptin (5 or 50 ng) into the PVN. Control application of sense (SON, 50 pmol) or a scrambled antisense Ob-R oligonucleotide (ASON2, 50 pmol) into the bilateral PVN promoted no discernible effect on Ob-R protein expression in the hypothalamus, on daily food intake, or on cardiovascular performance. Our results indicate that whereas the Ob-Rs in the PVN are involved in the tonic regulation of food intake, they might not be actively involved in the tonic regulation of cardiovascular functions. 相似文献
52.
Fu-Chou Cheng Jon-Son Kuo Wen-Ho Chang Dong-Juiing Juang Ying Shih Jeng-Shiow Lai 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1993,617(2)
The simultaneous measurement of homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in human plasma by an ultrafiltration and microbore high-performance liquid chromatography—electrochemical detection technique is established. Conventional preparation of blood is very tedious and time-consuming, but isocratic separation of the analytes in plasma ultrafiltrates using a microbore column could be achieved within 10 min. Hence, theoretically, over 140 analyses can be performed in a working day. The detection limit (signal-to-noise ratio = 3) of this method is about 0.1–0.5 pg per injection for all analytes. The required volume of plasma samples can be less than 100 μl. Hence, blood loss is minimal, especially in repeated blood sampling. This rapid, simple and sensitive method can, therefore, be used as a routine clinical tool in the simultaneous measurement of plasma homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid. 相似文献
53.
Girijavallabhan VM Chen L Dai C Feltz RJ Firmansjah L Li D Kim SH Kozlowski JA Lavey BJ Kosinski A Piwinski JJ Popovici-Muller J Rizvi R Rosner KE Shankar BB Shih NY Siddiqui MA Tong L Wong MK Yang DY Yang L Yu W Zhou G Guo Z Orth P Madison V Bian H Lundell D Niu X Shah H Sun J Umland S 《Bioorganic & medicinal chemistry letters》2010,20(24):7283-7287
Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles. 相似文献
54.
M P Kavanaugh M F Perutz G Fermi D T Shih R T Jones 《The Journal of biological chemistry》1989,264(19):11009-11013
Periodate-oxidized adenosine triphosphate (o-ATP), a ribose ring-opened dialdehyde derivative of ATP, reacts specifically with human deoxyhemoglobin to give a single major covalently modified product after reduction with sodium borohydride. This product, designated di-ATP Hb, was isolated using ion-exchange chromatography and shown to have incorporated two molecules of o-ATP/tetramer. Peptide mapping and x-ray crystallography at 2.8-A resolution indicate that a covalent adduct is formed between the ligand and residues Lys-82 EF6 of each beta chain in the organic phosphate-binding site of the molecule. di-ATP Hb exhibits a significantly decreased oxygen affinity (P50 = 20.8 mm Hg versus 5.8 mm Hg control; 50 mM 2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)-propane-1,3-diol, pH 7.4, 0.1 M C, 20 degrees C). The subunit cooper-activity of di-ATP Hb is also reduced (nmax = 1.9 versus 2.7 control). 相似文献
55.
San-Lang Wang Yue-Horng Yen Ing-Lung Shih Audrey Chingzu Chang Wen-Teish Chang Wen-Chieh Wu Yue-Der Chai 《Enzyme and microbial technology》2003,33(7):917-925
In this study, the agricultural waste was used to screen for an organism that is capable of producing enzymes for degrading xylan and cellulose. Results showed that Streptomyces actuosus A-151, isolated from northern Taiwan, produced β-xylanase when rice bran was used as the sole carbon source. Four xylanases, designated as FI-A, FI-B, FII-A, FII-B, were identified and purified from the culture filtrate of S. actuosus A-151. Their specific activities after purification were 41.3, 86.2, 20.4, 85.2 U/mg, respectively. The pH stability of the four enzymes was: FI-A, 5–8; FI-B, 3–8; FII-A, 5–9; and FII-B, 3–9. The optimum pH for FII-B was 4, and the others were near 5–6. The optimum temperatures for enzyme activities were 60 °C for FII-B, and 70 °C for the others. The thermal stability for all four enzymes were up to 60 °C. The molecular weights of FI-A, FI-B, FII-A, and FII-B xylanases were 30,000, 45,000, 26,000, and 20,000, respectively, by sodium dodecylsulfate–polyacrylamide gel electrophoresis and 30,000, 43,000, 25,000, and 21,000, respectively, by gel filtration. Addition of xylan, shrimp and crab shell powder, and orange peel to the culture medium was found to enhance the production of xylanase. 相似文献
56.
Since the first study of hypoxic response in plants with cDNA microarray in 2002, the number of hypoxia-responsive genes has grown to more than 2000. However, to date, only small numbers of hypoxia-responsive genes are known to confer hypoxic resistance. Most investigations in this area have focused on identifying which genes are responsive and then characterized how these genes are induced during hypoxia, but the roles of numerous genes in hypoxic response are still unknown. In our recent study, we demonstrated that a group of genes are induced by submergence to trigger plant immunity, which is a response to protect plants against a higher probability of pathogen infection during or after flooding. This work offered a brand new perspective, i.e., that hypoxia-responsive genes can be induced for reasons other than conferring hypoxic resistance. Possible reasons why these responses were triggered are discussed herein. 相似文献
57.
Mapping host range-specific oligonucleotides within genomes of the ecotropic and mink cell focus-inducing strains of Moloney murine leukemia virus. 总被引:5,自引:11,他引:5 下载免费PDF全文
The site of recombination of a mink cell focus-inducing strain (Mo-MuLV83) derived from an ecotropic Moloney murine leukemia virus (Mo-MuLV) was mapped by fingerprint analysis of the large RNase T1-resistant oligonucleotides, employing a two-dimensional gel electrophoresis method. Mo-MuLV83, in contrast to the ecotropic Mo-MuLV, demonstrated a broadened host range, i.e., growth not only on mouse cells but also on mink cells, and recombination involved the env gene function. The genomic RNA of these two viruses shared 42 out of a total of 51 to 53 large T1 oligonucleotides (81%) and possessed a similar subunit size of 36S. Most of these T1 oligonucleotides were mapped in their relative order to the 3' polyadenylic acid end of the viral RNA molecules. There were 10 common oligonucleotides immediately next to the 3' termini. A cluster of 7 (in Mo-MuLV83) or 10 (in Mo-MuLV) unique T1 oligonucleotides were mapped next to the common sequences at the 3' end, and they all appeared concomitantly in a polyadenylic acid-containing RNA fraction with a sedimentation coefficient slightly larger than 18S. Therefore, the env gene of Mo-MuLV was situated at a location approximately 2,000 to 4,000 nucleotides from the 3' end of the genomic RNA, and the gene order of Mo-MuLV appeared to be similar to that of the more rigorously determined avian oncornaviruses. cDNA(SFFV) specific for the xenotropic sequences in the spleen focus-forming virus RNA hybridized to the cluster of unique oligonucleotides of Mo-MuLV83 RNA. This suggests that the loci of recombination involve the homologous env gene region of a xenotropic virus. 相似文献
58.
NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways 总被引:2,自引:0,他引:2
Vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) play critical roles in vascular physiology and pathophysiology. We have demonstrated previously that NADPH oxidase-derived ROS are required for VEGF-mediated migration and proliferation of endothelial cells. The goal of this study was to determine the extent to which VEGF signaling is coupled to NADPH oxidase activity. Human umbilical vein endothelial cells and/or human coronary artery endothelial cells were transfected with short interfering RNA against the p47(phox) subunit of NADPH oxidase, treated in the absence or presence of VEGF, and assayed for signaling, gene expression, and function. We show that NADPH oxidase activity is required for VEGF activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 MAPK, but not ERK1/2 or JNK. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-VEGF receptor levels and involves the nonreceptor tyrosine kinase Src. DNA microarrays revealed the existence of two distinct classes of VEGF-responsive genes, one that is ROS-dependent and another that is independent of ROS levels. VEGF-induced, thrombomodulin-dependent activation of protein C was dependent on NADPH oxidase activity, whereas VEGF-induced decay-accelerating factor-mediated protection of endothelial cells against complement-mediated lysis was not. Taken together, these findings suggest that NADPH oxidase-derived ROS selectively modulate some but not all the effects of VEGF on endothelial cell phenotypes. 相似文献
59.
Chuen-Mao Yang Hsi-Lung Hsieh Chih-Chung Lin Ruey-Horng Shih Pei-Ling Chi Shin-Ei Cheng Li-Der Hsiao 《Molecular neurobiology》2013,47(3):1020-1033
Bradykinin (BK) has been shown to induce the expression of several inflammatory mediators, including reactive oxygen species (ROS) and matrix metalloproteinases (MMPs), in brain astrocytes. These mediators may contribute to neuronal dysfunction and death in various neurological disorders. However, the effects of multiple inflammatory mediators released from BK-challenged astrocytes on neuronal cells remain unclear. Here, we found that multiple factors were released from brain astrocytes (RBA-1) exposed to BK in the conditioned culture media (BK-CM), including ROS, MMP-9, and heme oxygenase-1 (HO-1)/carbon monoxide (CO), leading to neuronal cell (SK-N-SH) death. Exposure of SK-N-SH cells to BK-CM or H2O2 reduced cell viability and induced cell apoptosis which were attenuated by N-acetyl cysteine, indicating a role of ROS in these responses. The effect of BK-CM on cell viability and cell apoptosis was also reversed by immunoprecipitation of BK-CM with anti-MMP-9 antibody (MMP-9-IP-CM) or MMP2/9 inhibitor, suggesting the involvement of MMP-9 in BK-CM-mediated responses. Astroglial HO-1/CO in BK-CM induced cell apoptosis and reduced cell viability which was reversed by hemoglobin. Consistently, the involvement of CO in these cellular responses was revealed by incubation with a CO donor CO-RM2 which was reversed by hemoglobin. The role of HO-1 in BK-CM-induced responses was confirmed by overexpression of HO-1 in SK-N-SH infected with Adv-HO-1. BK-CM-induced cell apoptosis was due to the activation of caspase-3 and cleavage of PARP. Together, we demonstrate that BK-induced several neurotoxic factors, including ROS, MMP-9, and CO released from astrocytes, may induce neuronal death through a caspase-3-dependent apoptotic pathway. 相似文献
60.
Nonvascular role for VEGF: VEGFR-1, 2 activity is critical for neural retinal development. 总被引:10,自引:0,他引:10
G S Robinson M Ju S C Shih X Xu G McMahon R B Caldwell L E Smith 《FASEB journal》2001,15(7):1215-1217