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)

Primary cultures of rat hepatocytes produce tissue-type plasminogen activator (tPA) and plasminogen activator-inhibitor type 1 (PAI-1). Incubation of hepatocytes with 50 microM 8-(4-chlorophenylthio)cAMP (CPT-cAMP) results in a 4-fold increase in tPA activity, whereas the synthetic glucocorticoid dexamethasone (1 microM) causes a more than 90% decrease. In combination, dexamethasone completely overcomes the CPT-cAMP effect and markedly decreases PA activity. PAI-1 is induced by both CPT-cAMP and dexamethasone, and the effects of these agents are additive. Accumulation of tPA mRNA is increased more than 4-fold by CPT-cAMP and is greatly decreased by incubation with dexamethasone. Dexamethasone in combination with CPT-cAMP totally blocks this cAMP effect. The protein synthesis inhibitor cycloheximide does not prevent either the dexamethasone-induced decrease or the CPT-cAMP-induced increase in tPA message and, in fact, augments the cAMP-induced increase in tPA mRNA. Hepatocyte PAI-1 mRNA levels are increased 2-fold by incubation with either CPT-cAMP or dexamethasone; in combination, these effectors cause a 4-fold increase in PAI-1 mRNA. Cycloheximide alone causes a marked increase in PAI-1 mRNA, but does not block the induction by either CPT-cAMP or dexamethasone. We conclude that incubation of hepatocytes with CPT-cAMP induces tPA activity by increasing tPA mRNA accumulation and that dexamethasone causes a decrease in tPA activity by both decreasing tPA mRNA and increasing PAI-1 mRNA and activity. Concomitant protein synthesis is not required for the regulation of tPA or PAI-1 mRNA by either CPT-cAMP or dexamethasone, indicating a primary effect of these agents on gene transcription or mRNA stability.
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PMID:Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocytes. 253 89

Photocrosslinked nanogels with a hydrophobic core and hydrophilic shell are successfully fabricated with the goal of obtaining a biocompatible and biodegradable drug carrier for hydrophobic anticancer drugs. These nanogels are composed of amphiphilic triblock copolymers, poly(D,L-lactic acid)/poly(ethylene glycol)/poly(D,L-lactic acid) (PLA-PEG-PLA), with acrylated groups at the end of the PLA segments. The copolymers are synthesized by ring-opening polymerization and possess a low CMC (49.6 mg x L(-1)), which easily helps to form micelles by self-assembly. The acrylated end groups allow the micelles to be photocrosslinked by ultraviolet irradiation, which turn the micelles into nanogels. These nanogels exhibit excellent stability as a suspension in aqueous media at ambient temperature as compared to the micelles. Moreover, the size of the nanogels is easily manipulated in a range of 150 to 250 nm by changing the concentration of crosslinkers, e.g., ethylene glycol dimethacrylate, and ultraviolet light irradiation time. The nanogels achieve a high encapsulation efficiency and offer a steady and long-term release mechanism for the hydrophobic anticancer drug, CPT. It shows that these nanogels are useful for a hydrophobic anticancer drug-carrier system. [pictures: see text] Formation of the PLA-PEG-PLA nanogels.
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PMID:Amphiphilic poly(D,L-lactic acid)/poly(ethylene glycol)/poly(D,L-lactic acid) nanogels for controlled release of hydrophobic drugs. 1703 77

We report here a unique method of formulating camptothecin-polylactide (CPT-PLA) conjugate nanoparticles, termed nanoconjugates (NCs), through CPT/(BDI)ZnN(TMS)(2) [(BDI) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-bisalkyl)-imino)-2-pentene] mediated polymerization of lactide (LA) followed by nanoprecipitation. When CPT was used as the initiator to polymerize LA in the presence of (BDI)ZnN(TMS)(2), the polymerization was completed within hours with nearly 100% CPT loading efficiency and 100% LA conversion. CPT loading as high as 19.5% can be achieved for the CPT-polylactide (CPT-PLA) conjugate prepared at a LA/CPT ratio of 10. The steric bulk of the chelating ligands and the type of metals used had a dramatic effect on the initiation of the LA polymerization and the tendency of the ring-opening of the CPT lactone. The CPT/(BDI)ZnN(TMS)(2)-mediated LA polymerization yielded CPT-PLA conjugates with well-controlled molecular weights and narrow molecular weight distributions (1.02-1.18). The nanoprecipitation of CPT-PLA led to the formation of NCs around 100 nm in size with narrow particle size distributions. Sustained release of CPT from CPT-PLA NCs was achieved without burst release. CPT-PLA NCs were toxic to PC-3 cells with tunable IC(50) possible by adjusting the drug loading of the CPT-PLA NCs.
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PMID:Controlled synthesis of camptothecin-polylactide conjugates and nanoconjugates. 2000 Apr 58

PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent inflammatory mediator, is synthesized via the remodeling and the de novo route, key enzymes of which are acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAF-AT) and DTT-insensitive CDP-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT), respectively. PAF-acetylhydrolase (PAF-AH) and its extracellular isoform lipoprotein-associated phospholipase-A(2) (Lp-PLA(2)) catabolize PAF. This study evaluated PAF levels together with leukocyte PAF-CPT, lyso-PAF-AT, PAF-AH and Lp-PLA(2) activities in 106 healthy volunteers. Men had lower PAF levels and higher activity of both catabolic enzymes and lyso-PAF-AT than women (P-values <0.05). Age was inversely correlated with PAF levels in men (r=-0.279, P=0.06) and lyso-PAF-AT in women (r=-0.280, P=0.05). In contrast, Lp-PLA(2) was positively correlated with age (r=0.201, P=0.04). Moreover, PAF-CPT was positively correlated with glucose (r=0.430, P=0.002) in women. In addition, Principal Component Analysis revealed three PAF metabolic patterns: (i) increased activities of PAF-CPT and PAF-AH, (ii) increased activities of PAF-CPT and lyso-PAF-AT and (iii) increased activity of Lp-PLA(2). The present study underlines the complexity of PAF's metabolism determinants.
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PMID:PAF and its metabolic enzymes in healthy volunteers: interrelations and correlations with basic characteristics. 2207 87