Kích hoạt phản ứng sốc nhiệt trong mô hình tế bào chính của thoái hóa thần kinh motoneuron - Bằng chứng cho hiệu ứng bảo vệ và độc hại thần kinh
Tóm tắt
Việc tăng cường dược lý các protein sốc nhiệt (hsps) cứu sống các tế bào motoneuron khỏi chết tế bào trong một mô hình chuột bị bệnh teo cơ bên (amyotrophic lateral sclerosis). Tuy nhiên, mối quan hệ giữa sự gia tăng biểu hiện hsp và sự sống sót của tế bào thần kinh không đơn giản. Chúng tôi đã xem xét tác động của hai tác nhân dược lý kích thích phản ứng sốc nhiệt thông qua việc kích hoạt HSF-1, trên các tế bào motoneuron chính bị stress trong môi trường nuôi cấy. Mặc dù cả arimoclomol và celastrol đều kích thích biểu hiện của Hsp70, nhưng tác động của chúng lên các tế bào motoneuron chính trong môi trường nuôi cấy là khác nhau một cách đáng kể. Trong khi arimoclomol có tác dụng thúc đẩy sự sống sót, cứu sống các tế bào motoneuron khỏi sự chết tế bào do staurosporin và H2O2 gây ra, celastrol không những không bảo vệ các tế bào motoneuron chịu stress khỏi sự chết tế bào dưới cùng các điều kiện thí nghiệm, mà còn gây độc thần kinh và dẫn đến chết tế bào thần kinh. Việc nhuộm miễn dịch các môi trường nuôi cấy điều trị bằng celastrol cho hsp70 và caspase-3 đã kích hoạt cho thấy rằng điều trị bằng celastrol kích hoạt cả phản ứng sốc nhiệt và chuỗi phản ứng chết tế bào apoptosis. Những kết quả này chỉ ra rằng không phải tất cả các tác nhân kích hoạt phản ứng sốc nhiệt đều có thể mang lại tác dụng bảo vệ thần kinh.
Từ khóa
#dược lý #protein sốc nhiệt #motoneuron #thoái hóa thần kinh #bảo vệ thần kinh #độc hại thần kinhTài liệu tham khảo
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