Analysis of Lysophophatidylcholine-Induced Endothelial Dysfunction
| Autor: | W. Y. Kuo, Michael A. Levine, B. Drenger, Nicholas A. Flavahan, J. E. Freeman, T. N. Barnett |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Endothelium Arteriosclerosis Swine Blotting Western Bradykinin Stimulation GTP-Binding Protein alpha Subunits Gi-Go Biology Dinoprost Nitric Oxide Pertussis toxin Muscle Smooth Vascular Nitric oxide chemistry.chemical_compound Superoxides Internal medicine medicine Animals Virulence Factors Bordetella Endothelial dysfunction Pharmacology Lysophosphatidylcholines medicine.disease Vasodilation Lysophosphatidylcholine Endocrinology medicine.anatomical_structure Pertussis Toxin chemistry Mastoparan Endothelium Vascular Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cardiovascular Pharmacology. 28:345-352 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-199609000-00001 |
| Popis: | Endothelial dysfunction caused by the early atherosclerotic process or by endothelial exposure to atherogenic lipids, including lysophosphatidylcholine (lysoPC), is characterized by a selective impairment of responses mediated by the pertussis toxin-sensitive Gi-2 protein. Experiments were performed to analyze the mechanisms underlying this effect. Bradykinin (BK: Gi-2 protein-independent), serotonin (5-HT: Gi-2 protein-dependent), or direct activation of the G(i-2)-protein by mastoparan increased the release of endothelium-derived nitric oxide (EDNO) from porcine arterial endothelial cells (EC). LysoPC decreased the release of EDNO caused by 5-HT, but did not affect the response to BK or mastoparan. LysoPC did not increase production of superoxide radicals detected by lucigenin-enhanced chemiluminescence. Western blot analysis showed no difference in the level of immunoreactive Gi alpha-2 between control and lysoPC-treated cells. Activation of the Gi-2 protein by serotonergic or alpha 2-adrenoceptor stimulation decreased the pertussis toxin-catalyzed ADP-ribosylation of Gi alpha-2 protein in membranes from control but not lysoPC-treated cells. However, direct activation of the Gi-2 protein by mastoparan inhibited the ADP-ribosylation in membranes from control and lysoPC-treated cells. The toxin-catalyzed reaction was reduced in lysoPC-treated cells or lysoPC-treated membranes. LysoPC reduced the ability of endothelin to increase GTP gamma S binding to the Gi-2 protein but did not affect the activity of mastoparan. These results suggest that lysoPC inhibits a pertussis toxin-sensitive signaling pathway in EC by an effect consistent with receptor:Gi-2-protein uncoupling. |
| Databáze: | OpenAIRE |
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