Phosphatidylcholine breakdown in HDL3 stimulated platelets

Nazih, Hassan; Devred, D.; Martin-Nizard, Françoise; Fruchart, Jean Charles; Delbart, Christiane

doi:10.1016/0049-3848(90)90115-s

Cited by 19 publications

(15 citation statements)

References 14 publications

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“…When PKC inhibitors were added together with 50 fig/mL HDL 3 during the platelet activation step (C-H7, C-ST), they did not impair 1,2-diacylglycerol release, indicating that PKC is not involved in the early phase of 1,2-diacylglycerol release. These results are in good agreement with our previous data 4 indicating the involvement of PKC only in the late phase of 1,2-diacylglycerol generation. The use of inhibitors identifies this HDL,-induced desensitization of PLC activity at least in part as PKC mediated.…”

Section: Effects Of Protein Kinase Modulators On Hdl-induced Desensisupporting

confidence: 83%

“…In a previous article, 4 we demonstrated that HDL, (50 /xg/mL)-induced 1,2-diacylglycerol production in [ 3 H]-phosphatidylcholine-prelabeled platelets is not encoun- tered with HDL3 modified with tetranitromethane and is concentration dependent in the range of 0 to 0.7 mg/mL HDL3, with half-maximal and maximal responses occurring at 0.15 and 0.60 mg/mL HDL3, respectively. Stimulation with higher HDL3 concentrations resulted in a gradual decline in 1,2-diacylglycerol production.…”

Section: Discussionmentioning

confidence: 99%

“…Less than 1/200 of the radioactivity was associated with free lipids and nearly all the radioactivity with the phosphatidylcholine fraction. 4 …”

Section: [ 3 H] Phosphatidylcholine-prelabeled Plateletsmentioning

confidence: 99%

“…Higher HDL3 concentrations (1 mg/mL) are not able to trigger phosphatidylcholine hydrolysis, indicating a loss of responsiveness. 4 One major form of regulation of the activity of G protein-coupled receptors is desensitization, 6 -9 which is a general biological phenomenon whereby the response phospholipase C activity, whereas cAMP-dependent protein kinase inhibitor (1 ^tmol/L), heparin (100 nmol/L), or concanavalin A (0.25 mg/mL) were ineffective. HDL,-induced desensitization is accompanied at least by the phosphorylation of the 94-and 110-kD proteins.…”

mentioning

confidence: 99%

“…Higher HDL3 concentrations (1 mg/mL) are not able to trigger phosphatidylcholine hydrolysis, indicating a loss of responsiveness. 4 One major form of regulation of the activity of G protein-coupled receptors is desensitization, 6 -9 which is a general biological phenomenon whereby the response to a specific ligand wanes over time despite the continuous presence of the ligand. The impairment of receptor functions is linked to protein phosphorylation, which appears to be a key factor.…”

mentioning

confidence: 99%

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Protein kinase C-dependent desensitization of HDL3-activated phospholipase C in human platelets.

Nazih

Nazih‐Sanderson

Magret

et al. 1994

Arterioscler Thromb

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In isolated human platelets, exposure of subtraction 3 high-density lipoprotein (HDL,) binding sites to high concentrations of HDL, (1 mg/mL) causes rapid desensitization of HDL3 (50 jU,g/mL)-stimulated breakdown of phosphatidylcholine, as shown in approximately a 70% depression of the maximal 1,2-diacylglycerol release activity by phospholipase C. This desensitization is HDL, dose dependent (IC 50 , 150±20 ig/mL, n=6) and time dependent (t 1/2 , <30 seconds). It requires the binding of HDL,, as pretreatment of HDL, by tetranitromethane does not cause the desensitization of HDLj-induced phospholipase C activity. Permeabilization of human platelets with 10 /ig/mL digitonin, used to permit access of charged inhibitors to the cytosol, does not interfere with the pattern of HDLj (1 mg/mL) -induced desensitization of HDL, (50 /ig/mL)-stimulated phospholipase C. Inhibitors of protein kinase C (100 /umol/L H-7 and 10 /nmol/L staurosporine) markedly inhibit desensitization of HDL,-induced P revious studies have demonstrated that subtraction 3 high-density lipoprotein (HDL,) binding sites are present on platelet membranes. 13 Koller et al 3 have reported that the glycoprotein Ilb/IIIa complex, the inducible platelet fibrinogen receptor, is able to interact with lipoproteins. HDL3 was found to bind to either the 95-to 110-kD glycoprotein Ilia or to the 136-to 140-kD glycoprotein lib. Glycoprotein lib/ Ilia acts until now as a platelet HDL, binding site.Furthermore, HDL 3 binding sites are coupled to phospholipase C (PLC) through pertussis toxin-sensitive GTP binding proteins. 45 In human platelets, HDL 3 binding sites act via the PLC-mediated hydrolysis of phosphatidylcholine and the generation of 1,2-diacylglycerol, which activates the multifunctional enzyme protein kinase C (PKC). The HDL 3 -induced signaling pathway is recorded only when platelets are stimulated by low concentrations of HDL 3 (50 ixglmL). Higher HDL3 concentrations (1 mg/mL) are not able to trigger phosphatidylcholine hydrolysis, indicating a loss of responsiveness. 4 One major form of regulation of the activity of G protein-coupled receptors is desensitization, 6 -9 which is a general biological phenomenon whereby the response to a specific ligand wanes over time despite the continuous presence of the ligand. The impairment of receptor functions is linked to protein phosphorylation, which appears to be a key factor. Most often, homologous desensitization is accompanied by receptor phosphorylation, which triggers the process of functional uncoupling from G proteins. 1012 In addition, a rapid sequestration of the receptors away from the cell surface and a modulation of the expression of the receptor gene itself result in a net decrease in receptor number. 13 Whereas desensitization of the adrenergic system is rather well understood, less is known about receptors coupled to phosphatidylinositol or phosphatidylcholine turnover. 1417 Moreover, until now little has been known about HDL3 binding site regulation. Platelets therefore would seem to ...

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Section: Effects Of Protein Kinase Modulators On Hdl-induced Desensisupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

“…Less than 1/200 of the radioactivity was associated with free lipids and nearly all the radioactivity with the phosphatidylcholine fraction. 4 …”

Section: [ 3 H] Phosphatidylcholine-prelabeled Plateletsmentioning

confidence: 99%

mentioning

confidence: 99%

“…Higher HDL3 concentrations (1 mg/mL) are not able to trigger phosphatidylcholine hydrolysis, indicating a loss of responsiveness. 4 One major form of regulation of the activity of G protein-coupled receptors is desensitization, 6 -9 which is a general biological phenomenon whereby the response to a specific ligand wanes over time despite the continuous presence of the ligand. The impairment of receptor functions is linked to protein phosphorylation, which appears to be a key factor.…”

mentioning

confidence: 99%

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