Melatonin ức chế tác động gây chết tế bào phụ thuộc vào stress lưới nội chất thông qua AMPK trong tế bào gốc trung mô xương trong tổn thương oxy hóa của ty thể

Stem Cell Research & Therapy - 2020
Chunmei Fan1, Jianyu Feng2, Chi Tang1, Zhang Zhengbin3, Yingtong Feng4, Weixun Duan2, Mingming Zhai1, Zedong Yan1, Liwen Zhu5, Lele Feng2, Hanzhao Zhu2, Erping Luo1
1Department of Military Biomedical Engineering, Air Force Medical University, 169 Changle West Road, Xi’an, 710032, China
2Department of Cardiovascular Surgery, Xijing Hospital, Air Force Medical University, 127 Changle West Road, Xi’an, 710032, China
3Department of Geriatrics, The 8th Medical Center of Chinese PLA General Hospital, 17 Heishanhu Street, Beijing, 100091, China
4Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, 1 Xinsi Road, Xi’an, 710038, China
5Department of Cardiology, The First Affiliated Hospital of Xi’an Medical University, 277 Yanta West Road, Xi’an, 710077, China

Tóm tắt

Tóm tắt Giới thiệu Các tế bào gốc trung mô tuỷ xương (BMSCs) đã được sử dụng như là công cụ tế bào quan trọng trong các ứng dụng lâm sàng. Apoptosis do stress oxy hóa gây ra dẫn đến tỷ lệ sống sót thấp sau khi cấy ghép, và các cơ chế tiềm ẩn vẫn chưa được biết đến. Lưới nội chất (ER) và ty thể là các bào quan quan trọng được điều chỉnh bởi protein kinase được kích hoạt bằng adenosine monophosphate (AMPK), đặc biệt là trong tổn thương do stress oxy hóa. Melatonin có tác dụng chống oxy hóa bằng cách tiêu diệt các gốc tự do. Tại đây, chúng tôi nhằm mục đích khám phá liệu melatonin bảo vệ tế bào có giảm nhẹ sự rối loạn chức năng ty thể do stress ER thông qua AMPK ở BMSCs sau tổn thương do stress oxy hóa hay không. Phương pháp Các tế bào BMSCs chuột được tách chiết và tiếp xúc với H2O2 trong sự hiện diện hoặc không có melatonin. Sau đó, mức độ tổn thương tế bào, mức độ stress oxy hóa, chức năng ty thể, hoạt động AMPK, các protein liên quan đến stress ER, và các dấu hiệu apoptotic đã được đo lường. Thêm vào đó, việc tham gia của AMPK và stress ER trong sự bảo vệ của melatonin đối với BMSCs chống lại tổn thương do H2O2 được điều tra bằng cách sử dụng các chất kích thích và ức chế dược lý. Kết quả Melatonin cải thiện sự sống sót của tế bào và phục hồi chức năng của ty thể. Hơn nữa, melatonin điều chỉnh chặt chẽ việc phosphoryl hóa AMPK và các phân tử liên quan đến các con đường stress ER. Sự kích hoạt AMPK và ức chế stress ER sau khi bổ sung melatonin đã cải thiện tiềm năng màng ty thể (MMP), giảm thiểu tổn thương oxy hóa khởi phát từ ty thể, và cuối cùng ức chế các con đường tín hiệu apoptotic ở BMSCs. Việc kết hợp điều trị với N-acetyl-l-cysteine (NAC) đã tăng cường đáng kể tác dụng chống oxy hóa của melatonin. Quan trọng nhất, việc kích hoạt AMPK/ức chế stress ER dược lý đã thúc đẩy sự bảo vệ tế bào do melatonin gây ra, trong khi việc ức chế AMPK/khởi phát stress ER dược lý đã có tác dụng kháng cự lại tác động của melatonin đối với tổn thương do H2O2. Kết luận Dữ liệu của chúng tôi cũng tiết lộ một cơ chế tiềm năng chữa bệnh mới mà melatonin bảo vệ BMSCs khỏi apoptosis ty thể do stress oxy hóa, có thể thông qua việc điều chỉnh con đường AMPK-ER stress.

Từ khóa


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