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Các sản phẩm cuối glycation tiên tiến kích thích sự giải phóng yếu tố thần kinh nguồn gốc não từ tiểu cầu người thông qua sự kích hoạt kinaza gia đình Src
Tóm tắt
Yếu tố thần kinh nguồn gốc não (BDNF) có tác dụng tích cực không chỉ đối với các bệnh lý thần kinh do tiểu đường mà còn đối với tổn thương tim mạch. Có sự tranh luận về các mức BDNF huyết thanh ở bệnh nhân mắc bệnh tiểu đường (DM). Do BDNF có trong máu ngoại vi phong phú do tiểu cầu, điều này có thể đại diện cho sự rối loạn trong việc giải phóng BDNF từ tiểu cầu. Ở đây, chúng tôi tập trung vào các sản phẩm cuối glycation tiên tiến (AGEs), mà tăng cao ở bệnh nhân DM và có tác động bất lợi lên chức năng tim mạch. Mục tiêu của nghiên cứu này là làm sáng tỏ vai trò của AGEs trong việc điều chỉnh sự giải phóng BDNF từ tiểu cầu người. Tiểu cầu được thu thập từ máu ngoại vi của các tình nguyện viên khỏe mạnh được ủ với các nồng độ AGEs khác nhau (glycated-BSA) ở 37 °C trong 5 phút có hoặc không có BAPTA-AM, một chelator Ca2+ thấm qua tế bào, hoặc PP2, một chất ức chế mạnh của các kinaza gia đình Src (SFKs). Sự giải phóng và BDNF trong tế bào được đo bằng ELISA và tính toán. Sự phosphoryl hóa của Src và Syk, một kinaza hạ lưu của SFKs, trong các tiểu cầu kích thích đã được kiểm tra bằng phương pháp Western blotting và miễn dịch lắng đọng. AGEs kích thích sự giải phóng BDNF từ tiểu cầu người theo cách phụ thuộc vào liều lượng, điều này phụ thuộc vào Ca2+ nội bào và SFKs. Chúng tôi phát hiện rằng AGEs kích thích sự phosphoryl hóa của Src và Syk. AGEs kích thích sự giải phóng BDNF từ tiểu cầu người thông qua việc kích hoạt con đường Src-Syk-(có thể là phospholipase C)-Ca2+. Xem xét tác động độc hại của AGEs và vai trò bảo vệ của BDNF, có thể giả thuyết rằng sự giải phóng BDNF do AGEs kích thích là một hệ thống phòng thủ sinh học trong giai đoạn đầu của bệnh tiểu đường. Sự gia tăng mãn tính của AGEs có thể dẫn đến sự cạn kiệt hoặc giảm điều chỉnh BDNF trong tiểu cầu trong quá trình tiến triển của DM.
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#yếu tố thần kinh nguồn gốc não #sản phẩm cuối glycation #tiểu cầu người #bệnh tiểu đường #kích hoạt kinaza SrcTài liệu tham khảo
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