Sự phân hủy chromatin bậc cao do H2O2 gây ra: Một cơ chế mới của độc tính gen do oxy hóa

Springer Science and Business Media LLC - Tập 28 - Trang 57-60 - 2003
Gregory W. Konat1
1Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, USA

Tóm tắt

Độc tính gen của các loài oxy phản ứng (ROS) đã được xác định rõ ràng. Cơ chế cơ bản liên quan đến sự oxy hóa DNA bởi ROS. Tuy nhiên, chúng tôi gần đây đã chỉ ra rằng hydrogen peroxide (H2O2), môi giới chính của stress oxy hóa, cũng có thể gây ra tổn thương bộ gen một cách gián tiếp. Cụ thể, H2O2 ở các nồng độ liên quan đến bệnh lý nhanh chóng kích thích sự phân hủy chromatin bậc cao (HOCD), tức là sự cắt bỏ enzym các vòng chromatin và các oligomere của chúng tại các vùng gắn vào ma trận. Việc kích hoạt endonuclease xúc tác cho HOCD là một sự kiện tín hiệu được kích hoạt một cách đặc hiệu bởi H2O2. Sự kích hoạt này không phải do sự gia tăng ion canxi, nhưng nồng độ canxi nội bào ở trạng thái nghỉ là cần thiết để duy trì endonuclease ở dạng hoạt động. Mặc dù HOCD do H2O2 gây ra có thể phá hủy hiệu quả bộ gen dẫn đến cái chết tế bào, nhưng dưới các điều kiện stress oxy hóa không chết, HOCD do H2O2 gây ra có thể là nguồn gốc chính của các đột biến soma.

Từ khóa

#oxy hóa #độc tính gen #hydrogen peroxide #phân hủy chromatin #tổn thương bộ gen #đột biến soma

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