Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic lipids), lost both the stimulatory action on PAI-1 and the inhibitory action on t-PA. The extracted lipid from the incubated albumin, which has been found to accept the hydrophilic lipids from Ox-LDL, gained the stimulatory action on PAI-1 and the inhibitory action on t-PA. Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC. The incubation with synthetic palmitoyl LPC (10 microM) stimulated PAI-1 release by 85 +/- 7% of control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. 833 Mar 76

In a previous study (Latron et al. 1991. Arterioscler. Thromb. 11: 1821-1829) we have shown that oxidized low density lipoproteins (ox-LDL) stimulated the synthesis and secretion of plasminogen activator inhibitor-1 (PAI-1) by human umbilical vein endothelial cells (HUVEC) in culture. The present study is intended to give insight into the intracellular process responsible for this stimulation. The HUVEC lipids were labeled for 16 h with [3H]arachidonate and incubated either with native LDL (n-LDL) or ox-LDL for various times (15, 30, 60 min). Compared with unstimulated cells (no LDL added), ox-LDL induced a significant increase in the intracellular level of unesterified [3H]arachidonate, concomitantly with a significant decrease of the phosphatidylinositol fraction. The most marked effect was observed at 30 min and was significantly much less with n-LDL. Phospholipase inhibitors (4-bromophenacylbromide and mepacrine) added to the culture medium completely prevented the ox-LDL-induced stimulation of phosphatidylinositol degradation, [3H]arachidonate release, and PAI-1 secretion. HUVEC possess both phospholipase C and A activities and a high lysophospholipase activity, the phospholipase A pathway being in vitro more sensitive to inhibition by 4-bromophenacylbromide than the phospholipase C pathway. These results suggest that the stimulation of PAI-1 secretion by ox-LDL is mediated by the hydrolysis of membrane phosphatidylinositol through the activation of phospholipase A.
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PMID:Phosphatidylinositol turnover during stimulation of plasminogen activator inhibitor-1 secretion induced by oxidized low density lipoproteins in human endothelial cells. 844 34