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Những khiếm khuyết trong quá trình Glycolytic và Oxy hóa phosphoryl hóa xuất hiện trước khi phát triển tình trạng lão hóa ở tế bào nội mô vi mạch não người
Tóm tắt
Sự thay đổi trong các con đường năng lượng ty thể và glycolytic liên quan đến lão hóa có thể góp phần vào rối loạn mạch máu não. Chúng tôi đã nghiên cứu tác động của lão hóa đến năng lượng của tế bào nội mô vi mạch não người (HBMECs) bằng cách so sánh các tế bào trẻ (loại 7–9), tiền lão hóa (loại 13–15) và lão hóa (loại 20–21). Những tế bào HBMECs tiền lão hóa thể hiện chiều dài telomere giảm và hoạt động telomerase không thể phát hiện mặc dù các dấu hiệu của sự lão hóa không bị ảnh hưởng. Năng lượng sinh học trong HBMECs được xác định bằng cách đo tỷ lệ tiêu thụ oxy (OCR) và tỷ lệ acid hóa ngoại bào (ECAR). Sản xuất ATP tế bào trong HBMECs trẻ chủ yếu phụ thuộc vào glycolysis với glutamine là nhiên liệu ưa thích cho phosphoryl hóa oxy hóa ty thể (OXPHOS). Ngược lại, HBMECs tiền lão hóa thể hiện sự đóng góp ngang bằng cho tỷ lệ sản xuất ATP từ glycolysis và OXPHOS với việc sử dụng đều glutamine, glucose và axit béo làm nhiên liệu cho ty thể. So với tế bào trẻ, HBMECs tiền lão hóa cho thấy tỷ lệ sản xuất ATP tổng thể thấp hơn đặc trưng bởi sự đóng góp giảm sút từ glycolysis. Những khiếm khuyết của glycolysis thể hiện ở các tế bào tiền lão hóa bao gồm glycolysis cơ bản giảm, glycolysis bù đắp và acid hóa không glycolytic. Hơn nữa, các khiếm khuyết trong hô hấp ty thể ở các tế bào tiền lão hóa liên quan đến sự giảm hô hấp tối đa và khả năng dự trữ hô hấp nhưng OCR cơ bản và liên quan đến sản xuất ATP vẫn còn nguyên vẹn. Tuy nhiên, sự rò rỉ proton và hô hấp không ty thể không thay đổi ở HBMECs tiền lão hóa. HBMECs ở loại 20–21 thể hiện sự biểu hiện của các dấu hiệu lão hóa và duy trì những khiếm khuyết tương tự trong glycolysis và OXPHOS trở nên tồi tệ hơn. Do đó, lần đầu tiên, chúng tôi đã mô tả một cách toàn diện năng lượng sinh học của HBMECs tiền lão hóa để xác định những thay đổi trong các con đường năng lượng có thể góp phần vào quá trình lão hóa.
Từ khóa
#lão hóa #tế bào nội mô vi mạch não người #glycolysis #phosphoryl hóa oxy hóa #năng lượng sinh họcTài liệu tham khảo
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