Mizutani Daisuke, Tokuda Haruhiko, Onuma Takashi, Uematsu Kodai, Nakashima Daiki, Ueda Kyohei, Doi Tomoaki, Enomoto Yukiko, Matsushima-Nishiwaki Rie, Ogura Shinji, Iida Hiroki, Kozawa Osamu, Iwama Toru
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan.
Biosci Biotechnol Biochem. 2022 Jan 24;86(2):185-198. doi: 10.1093/bbb/zbab201.
Amyloid β protein deposition in cerebral vessels, a characteristic of Alzheimer's disease, is a risk factor for intracerebral hemorrhage. Amyloid β protein directly modulates human platelet function; however, the exact mechanism of action is unclear. Therefore, we investigated the effects of amyloid β protein on human platelet activation using an aggregometer with laser scattering. Amyloid β protein decreased platelet aggregation induced by thrombin receptor-activating protein, but not by collagen and ADP. Amyloid β protein also suppressed platelet aggregation induced by SCP0237 and A3227. Platelet-derived growth factor-AB secretion and phosphorylated-heat shock protein 27 release by thrombin receptor-activating protein were inhibited by amyloid β protein. Additionally, thrombin receptor-activating protein-induced phosphorylation of JNK and p38 MAP kinase was reduced by amyloid β protein. Collectively, our results strongly suggest that amyloid β protein negatively regulates protease-activated receptor-elicited human platelet activation. These findings may indicate a cause of intracerebral hemorrhage due to amyloid β protein.
淀粉样β蛋白在脑血管中的沉积是阿尔茨海默病的一个特征，也是脑出血的一个危险因素。淀粉样β蛋白直接调节人类血小板功能；然而，确切的作用机制尚不清楚。因此，我们使用激光散射凝集仪研究了淀粉样β蛋白对人类血小板活化的影响。淀粉样β蛋白可降低凝血酶受体激活蛋白诱导的血小板聚集，但对胶原蛋白和ADP诱导的血小板聚集没有影响。淀粉样β蛋白还可抑制SCP0237和A3227诱导的血小板聚集。淀粉样β蛋白可抑制凝血酶受体激活蛋白诱导的血小板衍生生长因子-AB分泌和磷酸化热休克蛋白27释放。此外，淀粉样β蛋白可降低凝血酶受体激活蛋白诱导的JNK和p38丝裂原活化蛋白激酶的磷酸化。总体而言，我们的结果有力地表明，淀粉样β蛋白对蛋白酶激活受体引发的人类血小板活化具有负调节作用。这些发现可能提示了淀粉样β蛋白导致脑出血的一个原因。
