Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enzymes considered to be markers for neurons (angiotensin converting enzyme, thermolysin-like metalloendopeptidase, alanine aminopeptidase, and glutamate-oxaloacetate transaminase), glia (glutamine synthetase, pyruvate carboxylase, and beta-glucuronidase), and endothelial cells (alkaline phosphatase and plasminogen activator) were measured in caudate nucleus from 10 sudden death controls, eight agonal state controls, and 16 Huntington's disease patients. Glutamate-oxaloacetate transaminase was slightly reduced by agonal state. The four enzymes with a neuronal distribution were all correlatively reduced in Huntington's disease caudate nucleus. Glutamine synthetase activity was reduced and beta-glucuronidase mean activity increased over twofold in Huntington's disease caudate nucleus, with the two enzyme activities being inversely related. Pyruvate carboxylase was markedly affected by agonal state and was very variable in Huntington's disease caudate nucleus. The two endothelial enzymes were unaltered in Huntington's disease caudate nucleus. The findings are indicative of neuronal loss, an increased proportion of altered glia, and also of maintained vasculature in Huntington's disease caudate nucleus. Measurement of enzyme activities can help to delineate the types of cell altered in Huntington's disease.
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PMID:Changes in nine enzyme markers for neurons, glia, and endothelial cells in agonal state and Huntington's disease caudate nucleus. 287 90

The proteolytic activities of human tumor cell lines deriving from bronchial squamous cell carcinoma, a lung metastasis of an embryonal rhabdomyosarcoma and a pleural mesothelioma were measured by use of chromogenic substrates. N-acetyl-alanine aminopeptidase activity, plasminogen activator activity, H-D-Ile-Pro-Arg-p-NA splitting activity as well as plasmin-like activity, cathepsin G-like activity and plasma-kallikrein-like activity were found in cell lysates. The enzymatic activity of N-acetyl-alanine aminopeptidase, plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity changed during culturing. Plasminogen activator and H-D-Ile-Pro-Arg-p-NA splitting activity decreased to very low values, whereas N-acetyl-alanine aminopeptidase activity leveled at 1 x 10(-5) mU/cell. Unlike other proteolytic activities, plasminogen activator was released into the medium. Plasminogen activator activity could be measured in culture medium which contained no fetal calf serum.
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PMID:Proteolytic activity of human tumor cell lines deriving from bronchial squamous cell carcinoma, pulmonary metastasis of rhabdomyosarcoma and pleural metastasis of mesothelioma. 332 2

Cellular proteases are those proteases that are localized in the cytoplasm and on the cell surface, but not those secreted into the extracellular matrix. Proteases localized on the cell surface play a specific role in the invasion process of malignant tumor cells. These are activated by a relatively complicated cascade in which different cathepsins, the plasminogen activator system, plasmin, and the matrix metalloproteinases, including the membrane-type matrix metalloproteinases, play a major role. This article places emphasis on the biologic function and oncologic significance of cathepsins B and L, as well as on the urokinase plasminogen activator and the membrane-type matrix metalloproteinases localized on the cell surface. Recent investigations on these factors revealed that they are dependent on each other, such that the upregulation or downregulation also causes alterations in the regulation of the other factors. This fact alone elucidates the complexity of this system. Moreover, there is growing evidence that other proteases hitherto known to have other functions, e.g. as signal proteases in the immunologic system, may be important for invasion provesses. To provide an example of this, we describe the invasive potential of aminopeptidase N (APN/CD13). These recent results, which shed light on the role of further proteases in invasion processes, clearly show the complexity of this proteolytic system. Against this biologic background, it seems not to be promising to establish single proteases as distinct parameters for the prognosis of the metastatic potential of malignant tumors.
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PMID:[Cellular proteases and invasion]. 1121 51

Certain tumor cells and most tumor endothelial cells overexpress a membrane-spanning molecule, aminopeptidase N (CD13) isoform, which is the receptor for peptides containing the Asn-Gly-Arg (NGR) motif. NGR-modified docetaxel (DTX)-loaded PEG-b-PLA polymeric micelles (NGR-PM-DTX) were firstly developed and tested in vitro and in vivo, while DTX-loaded polymeric micelles (PM-DTX) and free DTX were used as controls. The NGR-PM-DTX containing DTX were about 35 nm in diameter with spherical shape and high encapsulation efficiency. It was demonstrated quantitatively by the spectrophotofluorometry and qualitatively by the confocal image analysis that NGR facilitates the uptake of micelles by CD13-overexpressed tumor cells (fibrosarcoma, HT1080) and endothelial cells (human umbilical vein endothelial cells, HUVEC). Free NGR inhibited cellular uptake of NGR-PM-DTX, revealing the mechanism of receptor-mediated endocytosis. Higher cytotoxicity toward HT1080 cells and more efficient inhibition of HUVEC proliferation were also observed in NGR-PM-DTX groups, which were consistent well with the observation of cellular uptake. In BALB/c mice bearing HT1080 tumor xenografts, stronger antitumor efficacy and less body weight changes were shown in NGR-PM-DTX group, with good correlation between in vitro and in vivo. Therefore, it was concluded that NGR-PM could be a potential vehicle for delivering hydrophobic chemotherapeutic agents to CD13-overexpressing tumors.
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PMID:NGR-modified micelles enhance their interaction with CD13-overexpressing tumor and endothelial cells. 1947 Mar 94

The efficient delivery of therapeutic gene into cells of interest is a critical challenge to broad application of non-viral vectors. The approach of introducing ligands that lead gene vectors to target caveolae-mediated endocytosis on nanoparticle surface might serve as a promising strategy for the effective gene transfection. Recently, in an attempt to enhance the possibility of caveolae-mediated endocytosis, we fabricated a peptide-targeted gene vector for highly efficient receptor-mediated intracellular delivery. Cyclic Asn-Gly-Arg (cNGR) peptide was used to target gene loaded poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) to HUVEC over-expressing CD13. Using 6-lauroxyhexyl lysinate (LHLN) as cationic surfactant, cNGR modified PLA-PEG NPs (cNGR-PEG-PLA NPs) were capable of complexing and compacting DNA into homogeneous small-sized complexes (<200nm) with positive charge (~10mV). Fortunately, the results of in vitro cellular uptake tests and mechanism studies were consistent with our original hypothesis. The cNGR peptide presented on nanoparticles' surface could specifically mediate the fast and efficient internalization of cNGR-PEG-PLA NPs into HUVEC. Moreover, free cNGR inhibited their intracellular uptake into HUVEC revealing the mechanism of receptor-mediated endocytosis. Furthermore, the inspiring results of the mechanism studies and transfection assays demonstrated that caveolae-mediated endocytosis was indeed mainly involved in the internalization of cNGR-PEG-PLA NPs into HUVEC and led to significant gene transfection efficiency in contrast with cNGR non-modified PLA-PEG NPs. Given such encouraging and favorable properties including biocompatibility, high transfer efficiency, low cytotoxicity, and fast uptake by nondestructive endocytic pathways, cNGR-PEG-PLA NPs could be a promising carrier for the intracellular delivery of therapeutic agents.
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PMID:Enhanced gene transfection efficiency in CD13-positive vascular endothelial cells with targeted poly(lactic acid)-poly(ethylene glycol) nanoparticles through caveolae-mediated endocytosis. 2137 65