ISSN:
0021-9541
Schlagwort(e):
Life and Medical Sciences
;
Cell & Developmental Biology
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Biologie
,
Medizin
Notizen:
Thrombin, a potent platelet activating agent, has previously been found to increase intracellular calcium levels and/or thromboxane A2 synthesis in leukemic cell lines exhibiting specific markers of the megakaryocyte/platelet lineage. However, its functional role on these cells has not been defined. As thrombin is implicated in the regulation of cellular proliferation or differentiation in various other cell types, we investigated the functional effects of thrombin on the megakaryoblastic MEG-01 cell line, and further explored its receptor coupling mechanisms on these cells. We observed that thrombin caused in 1% serum containing culture medium, a reduction in the proliferation of MEG-01 cells, without affecting their differentiation stage as determined by the expression of platelet glycoproteins GPIIb/IIIa and GPIb, FVIII-related-antigen and cell-size measurement, which are specific markers for megakaryocyte maturation. In increases in cAMP levels, and in inositol-trisphosphate formation and intracellular Ca2+ levels. All these responses required thrombin proteolytic activity. The lipoxygenase inhibitor, nordihydroguaiaretic acid, blunted thrombin-induced calcium increase without affecting thrombin-induced increase in cAMP levels, suggesting different thrombin coupling mechanisms with these two second messenger pathways. In addition, the inhibitory effect of thrombin on MEG-01 cell growth was mimicked by cAMP level enhancing agents such as forskolin, prostaglandin E1 and Bt2 cAMP. These results suggest the involvement of a cAMP-dependent mechanism in the thrombin-induced reduction in MEG-01 cell growth.
Zusätzliches Material:
8 Ill.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/jcp.1041500110
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