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991.
Kwok TT Chen P Liu PY Tang YC Kong SK Fung KP Choy YM 《Biological signals and receptors》2001,10(5):294-298
K24 capsular polysaccharide (K24-CPS), with a known structure of a repeating unit, was isolated from the capsule of Klebsiella pneumoniae serotype K24. The polysaccharide was found to suppress the proliferation of Ehrlich ascites tumour (EAT) cells in vitro, but did not alter the cell cycle distribution of cells. K24-CPS treatment reduced the tyrosine phosphorylation of some proteins in EAT cells. Furthermore, the treatment also decreased the expression of c-JUN, but had no effect on the levels of c-FOS and c-MYC. It is speculated that the growth suppression effect of K24-CPS may be related to its effect in down-regulating c-JUN expression. 相似文献
992.
993.
Banerjee K Deshpande S Zheng M Kumaraguru U Schoenberger SP Rouse BT 《Cellular immunology》2002,219(2):108-118
Herpetic stromal keratitis (HSK), resulting from ocular infection with herpes simplex virus (HSV), is thought to represent a T cell mediated immunopathologic lesion. Antigens recognized by the inflammatory T cells remain unresolved and non-TCR mediated activation of T cells (bystander activation) is considered as also involved. This report documents further evidence for the bystander activation mechanisms using three T cell transgenic RAG-/- mouse strains. Accordingly HSK occurred in PCC RAG-/-, P14 RAG-/-, and OT-1 RAG-/- mice. In none of the models could HSV specific T cell reactivity be demonstrated and animals were unprotected from lesion development by immunization prior to HSV ocular infection. The results support the role of bystander activation as a mechanism of T cell mediated immunopathology and show that CD8(+) as well as CD4(+) T cells can participate in HSK lesion development. 相似文献
994.
Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation 总被引:14,自引:0,他引:14
The heterochronic gene lin-28 of the nematode Caenorhabditis elegans controls the relative timing of diverse developmental events during the animal's larval stages. lin-28 is stage-specifically regulated by two genetic circuits: negatively by the 22-nt RNA lin-4 and positively by the heterochronic gene lin-14. Here, we show that lin-28 is repressed during normal development by a mechanism that acts on its mRNA after translation initiation. We provide evidence that lin-14 inhibits a negative regulation that is independent of the lin-4 RNA and involves the gene daf-12, which encodes a nuclear hormone receptor. The lin-4-independent repression does not affect the initiation of translation on the lin-28 mRNA, and like the lin-4-mediated repression, acts through the gene's 3'-untranslated region. In addition, we find that lin-4 is not sufficient to cause repression of lin-28 if the lin-4-independent circuit is inhibited. Therefore, the lin-4-independent circuit likely contributes substantially to the down-regulation of lin-28 that occurs during normal development. The role of lin-4 may be to initiate or potentiate the lin-4-independent circuit. We speculate that a parallel lin-4-independent regulatory mechanism regulates the expression of lin-14. 相似文献
995.
Li W Nadelman C Gratch NS Li W Chen M Kasahara N Woodley DT 《Experimental cell research》2002,273(2):219-228
Migration of human keratinocytes plays a critical role in the re-epithelialization of human skin wounds, the process by which the wound bed is resurfaced and closed by keratinocytes as it forms a new epidermis. While the importance of ECM components and serum factors in the regulation of keratinocytes motility is well established, the intracellular signaling mechanisms remain fragmentary. In this study, we investigated the role of protein kinase Cdelta (PKCdelta) signaling in the promotion of human keratinocyte migration by a collagen matrix and bovine pituitary extract. We found that pharmacological inhibition of the PKCdelta pathway completely blocks migration. Using a lentivirus-based vector system, which offers more than 90% gene transduction efficiency to human keratinocytes, we show that the kinase-defective mutant of PKCdelta (K376R) dramatically inhibits human keratinocyte migration. Furthermore, PKCdelta is activated in migrating human keratinocytes. These observations indicate for the first time that the PKCdelta pathway plays an important role in the control of human keratinocyte migration. 相似文献
996.
Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase 总被引:75,自引:0,他引:75
Vickers C Hales P Kaushik V Dick L Gavin J Tang J Godbout K Parsons T Baronas E Hsieh F Acton S Patane M Nichols A Tummino P 《The Journal of biological chemistry》2002,277(17):14838-14843
Human angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a zinc metalloprotease whose closest homolog is angiotensin I-converting enzyme. To begin to elucidate the physiological role of ACE2, ACE2 was purified, and its catalytic activity was characterized. ACE2 proteolytic activity has a pH optimum of 6.5 and is enhanced by monovalent anions, which is consistent with the activity of ACE. ACE2 activity is increased approximately 10-fold by Cl(-) and F(-) but is unaffected by Br(-). ACE2 was screened for hydrolytic activity against a panel of 126 biological peptides, using liquid chromatography-mass spectrometry detection. Eleven of the peptides were hydrolyzed by ACE2, and in each case, the proteolytic activity resulted in removal of the C-terminal residue only. ACE2 hydrolyzes three of the peptides with high catalytic efficiency: angiotensin II () (k(cat)/K(m) = 1.9 x 10(6) m(-1) s(-1)), apelin-13 (k(cat)/K(m) = 2.1 x 10(6) m(-1) s(-1)), and dynorphin A 1-13 (k(cat)/K(m) = 3.1 x 10(6) m(-1) s(-1)). The ACE2 catalytic efficiency is 400-fold higher with angiotensin II () as a substrate than with angiotensin I (). ACE2 also efficiently hydrolyzes des-Arg(9)-bradykinin (k(cat)/K(m) = 1.3 x 10(5) m(-1) s(-1)), but it does not hydrolyze bradykinin. An alignment of the ACE2 peptide substrates reveals a consensus sequence of: Pro-X((1-3 residues))-Pro-Hydrophobic, where hydrolysis occurs between proline and the hydrophobic amino acid. 相似文献
997.
998.
A naked plasmid with human pre-pro-insulin gene was transferred into skeletal muscle of diabetic rats by electric pulses and gene expression was detected. Blood glucose concentration was decreased from 24 mmol l–1 to 8.5 mmol l–1. Circulating insulin-like protein was increased significantly to 15–20 U ml–1, while that of the control group injected with the empty vector remained at less than 10 U ml–1. The low blood glucose concentration lasted for more than two months. These studies indicate that electroporational transfer of plasmid with human pre-pro-insulin gene into skeletal muscle could be a potential method of gene therapy for human diabetes mellitus. 相似文献
999.
Allen MP Xu M Linseman DA Pawlowski JE Bokoch GM Heidenreich KA Wierman ME 《The Journal of biological chemistry》2002,277(41):38133-38140
1000.
Jelicks LA Chandra M Shirani J Shtutin V Tang B Christ GJ Factor SM Wittner M Huang H Weiss LM Mukherjee S Bouzahzah B Petkova SB Teixeira MM Douglas SA Loredo ML D'Orleans-Juste P Tanowitz HB 《International journal for parasitology》2002,32(12):1497-1506
Chagas' disease is an important cause of cardiomyopathy. Endothelin-1, a vasoactive peptide has been implicated in the pathogenesis of chagasic cardiomyopathy. C57BL/6 x 129sv and CD1 mice were thus, infected with trypomastigotes of Trypanosoma cruzi (Brazil strain) and these infected mice were compared with infected mice treated with phosphoramidon. This compound inhibits endothelin-converting enzyme and neutral endopeptidases and does not affect the growth of the parasite in culture. Phosphoramidon was given in a dose of 10mg/kg for the initial 15 days post-infection None of the C57Bl/6 x 129sv mice died as a result of infection. However, there was marked myocardial inflammation and fibrosis in infected, untreated mice. The hearts of the infected, phosphoramidon-treated mice showed significantly less pathology. Cardiac magnetic resonance imaging of infected mice revealed right ventricular dilation that was less severe in those treated with phosphoramidon. Phosphoramidon-treated CD1 mice survived the acute infection. Transthoracic echocardiography demonstrated left ventricular dilation and reduced percent fractional shortening and relative wall thickness. These alterations were also attenuated as a result of phosphoramidon treatment. These data suggest that endothelin-1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin-1 and/or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas' disease. 相似文献