Calcium mobilization evoked by amyloid beta-protein involves inositol 1,4,5-triphosphate production in human...

We examined the effects of amyloid beta-protein (A beta) on Ca2+ mobilization in human platelets. The addition of A beta fragments 25-35 (A beta 25-35) gradually increased the cytoplasmic free Ca2+ concentration ([Ca2+]i). After the maximum response, [Ca2+]i decreased and then reached a sustained, higher level of [Ca2+]i. Similar effects were also observed with A beta 1-40, whereas 1-28 , 12-28 and 31-35 did not affect the Ca2+ response. In the absence of extracellular Ca2+, A beta 25-35 caused a transient increase in [Ca2+]i, which returned to the resting level. U73122, a phospholipase C inhibitor, completely abolished Ca2+ mobilization induced by thrombin and A beta 25-35. Furthermore, A beta enhanced the production of inositol 1,4,5-trisphosphate (IP3) in platelets. These findings suggest that Ca2+ mobilization induced by A beta 25-35 is due to phospholipase C activation and IP3 production.