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Phosphorylation và chuyển vị của Nrf2 thông qua Plk2 kích hoạt chống viêm thông qua tín hiệu p53/Plk2/p21cip1 trong tổn thương thận cấp tính
Tóm tắt
Plk2 là một yếu tố phản ứng với căng thẳng tế bào được kích thích trong phản ứng với stress oxy hóa. Tuy nhiên, vai trò của Plk2 trong tổn thương thận cấp tính (AKI) vẫn chưa được làm rõ. Chúng tôi trước đây đã phát hiện ra rằng Plk2 là một yếu tố tương tác của Nrf2 trong phản ứng với căng thẳng tế bào, vì Plk2 được điều hòa tăng lên trong mạng lưới phụ thuộc vào Nrf2. Tại đây, chúng tôi chỉ ra rằng nồng độ của p53, Plk2, p21cip1 và Nrf2 liên kết với cromatin đều được điều hòa tăng lên trong mô thận của chuột hoặc tế bào NRK52E được xử lý bằng cisplatin hoặc methotrexate. Việc tăng cường Plk2 bởi p53 dẫn đến sự gia tăng Nrf2 trong cả các phần tan và cromatin trong các tế bào NRK52E được xử lý bằng cisplatin. Nhất quán, việc tiêu hao Plk2 đã ức chế nồng độ của Nrf2. Đáng chú ý, Plk2 đã phosphoryl hóa trực tiếp Nrf2 tại Ser40, điều này đã tạo điều kiện cho sự tương tác của nó với p21cip1 và chuyển vị vào nhân tế bào để kích hoạt các yếu tố chống oxy hóa và chống viêm nhằm phản ứng với AKI. Tổng thể, những phát hiện này gợi ý rằng Plk2 có thể hoạt động như một điều hòa viên chống oxy hóa và chống viêm thông qua việc phosphoryl hóa và kích hoạt Nrf2 để bảo vệ tế bào thận khỏi các chất độc hại và vì vậy Plk2 và Nrf2 phối hợp làm việc để bảo vệ và duy trì sự sống của các tế bào thận trước các căng thẳng có hại.
Từ khóa
#Plk2 #Nrf2 #tổn thương thận cấp tính #phosphoryl hóa #p53Tài liệu tham khảo
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