Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of lipoprotein lipase on chylomicrons (CM) and very low density lipoproteins (VLDL) produces remnant lipoproteins (RLP) that are rich in triglycerides, cholesterol and apolipoprotein E (apo E). Apo E serves as a ligand for the LDL receptor and mediates uptake of RLP by macrophages, vascular wall and other cells that express the LDL receptor. Uptake of RLP can profoundly alter the physiology of cells and promote atherosclerosis and thrombosis. Like RLP, blood platelets also have roles in atherosclerosis and thrombosis; hence it is likely that RLP can influence platelet activity as well. Platelet aggregation was assessed by measuring the loss of single platelets. Apo E3/3-rich RLP derived from normal human plasma VLDL and CM were prepared by an immunoseparation method. At 2.5 to 10 microliters, RLP induced platelet aggregation that increased with the dose of RLP, but decreased it at 25 to 200 microliters. Unlike apo E3/3-rich RLP, apo E4/3 (heterozygous phenotype) rich RLP caused platelet aggregation in a dose-dependent manner, without producing a bell-shape dose-response relationship. Scanning electron microscopy revealed that activated platelets had adhered to and formed aggregates on the red cell membrane. The platelet response was unaffected by aspirin, but was inhibited by apyrase (an ADP scavenger), 2-chloroadenosine (a platelet ADP-receptor antagonist) and cilostazol, a phosphodiesterase type III inhibitor. It is thought that RLP cause leakage of ADP from red cells, which then mediates platelet aggregation.
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PMID:[Aggregation of human blood platelets by remnant-like lipoprotein particles]. 1121 76

As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted from Nf1+/- male-specific defects in cyclic AMP regulation, rather than from changes in purinergic receptor expression. Cyclic AMP elevation by phosphodiesterase blockade restored the male Nf1+/- microglia defects in P2Y-dependent membrane currents and process motility. Taken together, these data establish a sex-by-genotype interaction important to microglia function in the adult mouse brain.
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PMID:Neurofibromatosis 1 - Mutant microglia exhibit sexually-dimorphic cyclic AMP-dependent purinergic defects. 3273 84