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)

Sodium butyrate (NaB) can induce teratocarcinoma cell differentiation as retinoic acid (RA). However, the function of these two agents seems to be a little different [Kosaka et al., Exp Cell Res, 192:46-51, 1991]. F9 cells treated with NaB synthesize both tissue-type (tPA) and urokinase-type (uPA) plasminogen activator, though RA induces only tPA production. Urokinase-type PA is demonstrated to exist in association with membrane and to localize its activity to the close environment of the cell surface. This may cause the specific cell morphology and characteristics of differentiated F9 cells induced with NaB.
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PMID:Teratocarcinoma F9 cells induced to differentiate with sodium butyrate produce both tissue-type and urokinase-type plasminogen activators. 164 65

Treatment of tumor cells that have little if any metastatic potential with certain drugs that have little or no mutagenic activity has been found to result in marked phenotypic alterations of the cells, including development of a metastatic potential. We found that polar compounds and butyric acid, which are known to alter the expressions of normally silent genes, enhanced the lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells. This change was accompanied by increases in the activities of degradative enzymes such as glycosidases, cathepsin B, and plasminogen activator; adhesion of the cells to culture dishes, monolayers of endothelial cells, and a subendothelial matrix; and homotypic aggregation. The effects of these drugs in enhancing the lung-colonizing ability of the cells was found to be reversible, suggesting that it was due to epigenetic alterations. Other investigators have shown that treatment of nonmetastatic tumor cells with 5-azacytidine, which causes hypomethylation of DNA and activates normally silent genes, results in the emergence of a small number of clones with a heritable but unstable metastatic phenotype. These findings suggest that epigenetic mechanisms are involved in rapid cellular phenotypic diversification and tumor progression.
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PMID:Modification of the metastatic potential of tumor cells by drugs. 243 28

Treatment of cloned low-metastatic Lewis lung carcinoma cells (P-29) with dimethylsulfoxide or butyric acid resulted in enhancement of their lung-colonizing ability. This was accompanied with increases in cathepsin B activity, the production of plasminogen activator, and adhesiveness, mainly heterotypic adhesion (adhesion to monolayers of endothelial cells) of dimethylsulfoxide-treated cells and homotypic aggregation of butyric acid-treated cells. Treatment of P-29 cells with 8-bromoadenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP) also resulted in increases in cathepsin B activity and the production of plasminogen activator. However, it did not enhance either heterotypic adhesion or homotypic aggregation of the cells. The lung-colonizing ability of 8-bromo-cyclic AMP-treated P-29 cells was examined after their intravenous injection into male C57BL/6 mice. It was found that these cells did not have enhanced lung-colonizing ability. These results suggest that high activities of proteolytic enzymes such as cathepsin B and plasminogen activator in tumor cells are not sufficient alone for completing the metastatic process, but that other properties of tumor cells such as adhesiveness are also necessary.
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PMID:Effects of 8-bromoadenosine 3':5'-cyclic monophosphate on proteolytic enzymes, adhesiveness and lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells. 302 66

The lung-colonizing ability of low-metastatic Lewis lung carcinoma cells (P-29) was enhanced by their in vitro treatment with butyric acid and its sodium salt, sodium butyrate. Of the short chain fatty acids tested, butyric acid was the most effective in enhancing the lung-colonizing ability of P-29 cells; propionic acid and valeric acid were slightly effective, but acetic acid and caproic acid were ineffective. The enhancing effect of butyric acid on the lung-colonizing ability of P-29 cells was reversible, indicating that the result was the consequence of epigenetic alterations. Treatment of P-29 cells with butyric acid resulted in enhancement of secretion of plasminogen activator, cellular cathepsin B activity, and cellular adhesiveness. The phenotypes of cells treated with butyric acid were compared with those of cells treated with dimethyl sulfoxide, which was reported to enhance the lung-colonizing ability of P-29 cells. Significant differences were found in the phenotypes, especially that of cellular adhesiveness; that is, butyric acid enhanced mainly homotypic aggregation of the cells, while dimethyl sulfoxide enhanced mainly heterotypic adhesion, such as adhesion to monolayers of endothelial cells. In addition, butyric acid reversibly caused hyperacetylation of core histones in P-29 cells, while dimethyl sulfoxide did not.
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PMID:Effect of butyric acid on lung-colonizing ability of cloned low-metastatic Lewis lung carcinoma cells. 394 96

Human colonic epithelium is exposed to varying levels of sodium butyrate, which is derived from the bacterial fermentation of dietary carbohydrate. Sodium butyrate has several effects on colonic tumor cells in vitro, including arrest of cell growth and differentiation. In the present study we have found that, in addition to a reduction in cellular proliferation, sodium butyrate induces the transient expression of plasminogen activator inhibitor type-1 (PAI-1) in the LIM 2405 human colonic tumor cell. Approximately 40% of the PAI-1 secreted is biologically active as judged by the formation of higher molecular weight, SDS-resistant complexes with urokinase plasminogen activator (uPA). The enhanced PAI-1 biosynthesis was accompanied by an increase in PAI-1 mRNA levels. During the same time period, the amount of secreted uPA remained relatively constant, but the level of cell associated uPA decreased slowly and was accompanied by a decrease in uPA mRNA levels. The uPA receptor is synthesized constitutively by these cells, and was down-regulated at both the protein and mRNA levels in response to sodium butyrate. The results demonstrate that sodium butyrate can alter the balance of components of the plasminogen activator system in a manner which favours net decreased plasminogen activator activity and suggests a role for sodium butyrate in the regulation of extracellular proteolysis.
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PMID:Sodium butyrate differentially modulates plasminogen activator inhibitor type-1, urokinase plasminogen activator, and its receptor in a human colon carcinoma cell. 810 11

Sodium n-butyrate-induced flat reversion in v-K-ras oncogene-transformed rat kidney (KNRK) cells is associated with transcriptional activation of the p52PAI-1 gene (which encodes the type-1 inhibitor of plasminogen activator). Butyrate-initiated expression of p52PAI-1 mRNA and protein correlated with induced cell spreading and preceded development of cell-to-substrate focal adhesions. Such undersurface matrix contact structures, which are absent from parental KNRK cells, require proximal PAI-1 deposition for their stabilization. Stimulated p52PAI-1 expression by flat revertants (approximating 25-fold that of control cells) and the accompanying cytoarchitectural reorganization appeared to be programmed responses to butyrate as both events required de novo RNA and protein synthesis, metabolic characteristics consistent with a secondary pathway of gene regulation. To assess the relevance of p52PAI-1 induction to the process of flat reversion more critically, a molecular genetic approach was designed to maintain high-level constitutive p52PAI-1 synthesis in the absence of butyrate. KNRK cells transfected with a Rc/CMVPAI plasmid construct, in which expression of a p52PAI-1 cDNA insert was driven by enhancer-promoter sequences from the immediate-early gene of human cytomegalovirus, formed colonies comprised of flat-revertant-like cells with a greater frequency than did cells transfected with the Rc/CMV vector alone (24.8% and 1.7% respectively). Comparative analysis of randomly selected Rc/ CMVPAI clones indicated that a 10-fold increase in immunoreactive p52PAI-1 protein, relative to Rc/CMV isolates, correlated with generation of the flat phenotype. These data suggest that induced p52PAI-1 expression probably functions in the development of morphological revertants in the KNRK cell system.
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PMID:P52PAI-1 gene expression in butyrate-induced flat revertants of v-ras-transformed rat kidney cells: mechanism of induction and involvement in the morphological response. 902 Aug 77

The aerosol solvent extraction system (ASES) is a method based on solvent extraction using supercritical carbon dioxide for the preparation of microspheres. The ASES technology seems to be strongly affected by physico-chemical properties of biodegradable polymers, leading to incomplete or unsuccessful microsphere formation. The number of suitable polymers for ASES, such as poly(L-lactide) (L-PLA) and poly(beta-hydroxy-butyric acid) (PHB) is rather limited for unknown reasons. Therefore linear and novel branched polyesters were synthesized and subjected to the ASES process to explore the function property relationship. The properties of these polymers as well as of the ASES products were characterized by NMR spectroscopy, differential scanning calorimetry, light scattering, wide-angle X-ray scattering and scanning electron microscopy. It appears that high degrees of polymer crystallinity are the key factor for successful microsphere formation using the ASES process. Under the conditions investigated two types of polymers were especially suitable: semi-crystalline comb polyesters as well as comb polyesters in which crystallinity could be induced. These novel polymers are of particular interest for the ASES encapsulation technology since they combine beneficial properties both controlling drug release due to their three-dimensional architecture and faster biodegradability with sufficient mechanical stability to allow particle formation using supercritical carbon dioxide.
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PMID:Biodegradable semi-crystalline comb polyesters influence the microsphere production by means of a supercritical fluid extraction technique (ASES). 1064 May 80

We used biodegradable plastics as fermentation substrates for the filamentous fungus Aspergillus oryzae. This fungus could grow under culture conditions that contained emulsified poly-(butylene succinate) (PBS) and emulsified poly-(butylene succinate-co-adipate) (PBSA) as the sole carbon source, and could digest PBS and PBSA, as indicated by clearing of the culture supernatant. We purified the PBS-degrading enzyme from the culture supernatant, and its molecular mass was determined as 21.6 kDa. The enzyme was identified as cutinase based on internal amino acid sequences. Specific activities against PBS, PBSA and poly-(lactic acid) (PLA) were determined as 0.42 U/mg, 11 U/mg and 0.067 U/mg, respectively. To obtain a better understanding of how the enzyme recognizes and hydrolyzes PBS/PBSA, we investigated the environment of the catalytic pocket, which is divided into carboxylic acid and alcohol recognition sites. The affinities for different substrates depended on the carbon chain length of the carboxylic acid in the substrate. Competitive inhibition modes were exhibited by carboxylic acids and alcohols that consisted of C4-C6 and C3-C8 chain lengths, respectively. Determination of the affinities for different chemicals indicated that the most preferred substrate for the enzyme would consist of butyric acid and n-hexanol.
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PMID:Purification and characterization of a biodegradable plastic-degrading enzyme from Aspergillus oryzae. 1596 70

Photoreactive and cytocompatible polymer nanoparticles for immobilizing and releasing proteins were prepared. A water-soluble and amphiphilic phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-4-(4-(1-methacryloyloxyethyl)-2-methoxy-5-nitrophenoxy) butyric acid (PL)) (PMB-PL) was synthesized. The PMB-PL underwent a cleavage reaction at the PL unit with photoirradiation at a wavelength of 365 nm. Additionally, the PMB-PL took polymer aggregate in aqueous medium and was used to modify the surface of biodegradable poly(L-lactic acid) (PLA) nanoparticle as an emulsifier. The morphology of the PMB-PL/PLA nanoparticle was spherical and approximately 130 nm in diameter. The carboxylic acid group in the PL unit could immobilize proteins by covalent bonding. The bound proteins were released by a photoinduced cleavage reaction. Within 60s, up to 90% of the immobilized proteins was released by photoirradiation. From these results and with an understanding of the fundamental properties of MPC polymers, we concluded that PMB-PL/PLA nanoparticles have the potential to be used as smart carriers to deliver proteins to biological systems, such as the inside of living cells.
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PMID:Preparation of photoreactive phospholipid polymer nanoparticles to immobilize and release protein by photoirradiation. 2626 22