Zhangfei kích thích sự biểu hiện của thụ thể yếu tố tăng trưởng thần kinh, trkA, trong các tế bào u nguyên bào thần kinh và gây ra sự phân hóa hoặc apoptosis ở chúng

Journal of Neuro-Oncology - Tập 91 - Trang 7-17 - 2008
Ximena Valderrama1,2, Noreen Rapin1, Valerie M. K. Verge3, Vikram Misra1
1Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, Canada
2Instituto de Producción Animal, Facultad de Ciencias Agrarias, Universidad Austral de Chile, Valdivia, Chile
3Department of Anatomy and Cell Biology and Cameco MS Neuroscience Research Centre, University of Saskatchewan, Saskatoon, Canada

Tóm tắt

Sự tương tác giữa yếu tố tăng trưởng thần kinh (NGF) và thụ thể của nó—thụ thể kinase A liên quan đến tropomyosin (trkA)—điều chỉnh nhiều chức năng thần kinh, bao gồm sự phát triển đúng đắn của các tế bào cảm giác trong quá trình phát triển phôi, sự sống sót của các tế bào cảm giác và sự phân hóa cũng như apoptosis của các khối u thần kinh. Zhangfei là một yếu tố phiên mã được biểu hiện trong các tế bào thần kinh đã phân hóa. Vì chúng tôi có thể phát hiện Zhangfei trong các tế bào thần kinh trưởng thành nhưng không thấy trong các tế bào khối u thần kinh, chúng tôi đã giả thuyết rằng sự biểu hiện ngoại lai của protein này trong các tế bào medulloblastoma có thể sẽ kích thích sự phân hóa của các tế bào đó. Chúng tôi cho thấy rằng trong các tế bào medulloblastoma ONS-76, resveratrol, một chất kích thích apoptosis và phân hóa, đã làm tăng biểu hiện của Zhangfei, trkA và Gen Phản ứng Tăng trưởng sớm 1 (Egr1), một gen thường được kích hoạt bởi tín hiệu NGF–trkA. Các tế bào ONS-76 ngừng phát triển ngay sau khi điều trị bằng resveratrol. Trong khi việc kích thích Zhangfei trong các tế bào điều trị bằng resveratrol là nhẹ nhưng nhất quán, việc nhiễm các tế bào medulloblastoma đang phát triển tích cực bằng một vector adenovirus mang Zhangfei đã bắt chước một số hiệu ứng của resveratrol. Zhangfei được biểu hiện ngoại lai trong các tế bào ONS-76 đã dẫn đến sự gia tăng biểu hiện của trkA và Egr1, phosphoryl hóa kinase điều hòa tín hiệu ngoại bào (Erk1), và gây ra các tế bào ONS-76 xuất hiện các dấu hiệu của sự apoptosis. UW228, một dòng tế bào medulloblastoma khác, cũng nhạy cảm với các tác động ức chế của resveratrol và Zhangfei. Ngược lại, trong khi resveratrol ức chế sự phát triển của các tế bào sợi diploid người (MRC5), Zhangfei có tác động tương đối nhỏ tới các tế bào này.

Từ khóa

#yếu tố tăng trưởng thần kinh #trkA #Zhangfei #u nguyên bào thần kinh #apoptosis #phân hóa

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