Huntingtin đột biến gây quá tải sắt thông qua việc tăng cường IRP1 trong bệnh Huntington

Springer Science and Business Media LLC - Tập 8 - Trang 1-12 - 2018
Li Niu1, Cuifang Ye1,2, Yun Sun1, Ting Peng1,2,3, Shiming Yang1, Weixi Wang1, He Li1,2,3
1Department of Histology and Embryology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
2Institute for Brain Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
3Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

Tóm tắt

Sự tích tụ sắt trong hạch nền kèm theo mất tế bào thần kinh ở bệnh nhân mắc bệnh Huntington (HD) và các mô hình bệnh ở chuột. Sự rối loạn cân bằng sắt não trong HD xảy ra trước khi có các dấu hiệu lâm sàng. Do đó, việc điều tra cơ chế tích tụ sắt là rất quan trọng để hiểu vai trò của nó trong quá trình sinh bệnh. Sắt trong não chuột biến đổi N171-82Q HD được phát hiện bằng cách sử dụng thuốc nhuộm Perls được tăng cường bằng Diaminobenzidine. Các protein điều hòa cân bằng sắt bao gồm protein phản ứng sắt 1 (IRP1), transferrin (Tf), ferritin và thụ thể transferrin (TfR) đã được xác định bằng kỹ thuật western blotting và hóa học miễn dịch, và các mức độ biểu hiện tương đối của RNA đã được đo bằng RT-PCR trên cả chuột biến đổi N171-82Q HD và tế bào HEK293 biểu hiện đầu N-terminal của huntingtin. Lượng sắt tăng lên trong vùng hạt và vỏ não của chuột biến đổi N171-82Q HD. Phân tích các protein điều hòa cân bằng sắt đã cho thấy sự gia tăng biểu hiện của IRP1, Tf, ferritin và TfR trong vùng hạt và vỏ não của chuột N171-82Q. Kết quả tương tự cũng được ghi nhận ở tế bào HEK293 biểu hiện đầu N-terminal của huntingtin đột biến chứa 160 lặp lại CAG. Chúng tôi kết luận rằng huntingtin đột biến có thể gây ra các con đường điều hòa sắt bất thường bằng cách tăng cường biểu hiện IRP1 trong bệnh Huntington, điều này gợi ý về một mục tiêu trị liệu tiềm năng.

Từ khóa

#Bệnh Huntington #hạch nền #tích tụ sắt #IRP1 #điều hòa cân bằng sắt

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