2000 Fiscal Year Final Research Report Summary
Studies on the function and the regulation of expression of platelet membrane protein GPIV (CD36)
| Project/Area Number |
09672346
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory medicine
|
|---|
| Research Institution | Asahikawa Medical College |
|---|
Principal Investigator |
HAYASHI Yukiko Asahikawa Medical College, Dept. of Medicine, Assistant Prof, 医学部, 講師 (50125407)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOHMURA Chikashi Asahikawa Medical College, Dept. of Medicine, Instructor, 医学部, 助手 (40261408)
KAWABATA Isao Asahikawa Medical College, Dept. of Medicine, Instructor, 医学部, 助手 (50195129)
|
|---|
| Project Period (FY) |
1997 – 2000
|
| Keywords | Platlet / Signal transduction / PKC / Arachidonic acid / CD36 |
|---|
| Research Abstract |
We have studied the effects of platelet membrane protein CD36 on the platelet signal transduction using CD36 defective platelets. One of the reported roles of CD36 is the transporter of unsaturated fatty acids. Compared to normal ones little characteristic responses of CD36 defective platelets have been reported. Arachidonic acid (AA), one of the unsaturated fatty acid, has pivotal role in platelet aggregation through its metabolite TxA2. We observed that under the decreasing store Ca2+ conditions CD36 defective platelets showed clear differences in the reactions where AA metabolites have more essential roles. We found that AA inhibits platelet aggregation induced by its metabolites TxA2. The IC50 of AA for normal platelets was 26.5±12.2 μM,and that for C36 defective platelets was 105±44 μM respectively. These results corroborate the role of CD36 as fatty acid transporter. This is the first report on the impaired functions of CD36 defective platelets. AA and other unsaturated fatty acids activate Ca2+ independent PKC in the cytosol independently of membrane lipids and cytosolic Ca2+ Physiological significances of the PKC isotypes have not been clearly understood. Hence the mechanisms of the inhibiting effects of AA were next studied. It was confirmed that AA inhibits PLCβ activation through serine phosphorylation by Ca2+ independent PKC.Consequently the Ca2+ dependent PKC closely connected to aggregation are not activated. Thus PKC isotypes are linked to each other leading to the physiologically proper responses of platelets. More important point is that AA itself regulates reactions induced by its descendants through the PKC isotypes.
|
