Vai trò của Các Thụ thể Beta-adrenergic và Đường tín hiệu Sirtuin trong Tim trong Quá trình Lão hóa, Suy Tim, và Thích nghi với Căng thẳng

Springer Science and Business Media LLC - Tập 38 - Trang 109-120 - 2017
Regina Celia Spadari1,2, Claudia Cavadas3, Ana Elisa T. Saturi de Carvalho1, Daniela Ortolani1,4, Andre Luiz de Moura1, Paula Frizera Vassalo4,5
1Laboratory of Stress Biology, Department of Biosciences, Campus Baixada Santista, Universidade Federal de São Paulo (UNIFESP), Santos, Brazil
2Departamento de Biociências / Campus Baixada Santista, UNIFESP, Santos, Brazil
3Center for Neurosciences and Cell Biology (CNC) and School of Pharmacy, University of Coimbra, Coimbra, Portugal
4Department of Physiological Science, Universidade Federal Do Espírito Santo (HUCAM, UFES), Vitória, Brazil
5University Hospital Cassiano Antônio de Moraes, Universidade Federal Do Espírito Santo (HUCAM, UFES), Vitória, Brazil

Tóm tắt

Trong tim, các hiệu ứng catecholamine xảy ra thông qua việc kích hoạt các thụ thể beta-adrenergic (β-ARs), chủ yếu là các loại beta 1 (β1-AR) và beta 2 (β2-AR), cả hai đều liên kết với protein Gs để kích hoạt con đường tín hiệu adenylyl cyclase. Các β2-AR cũng có thể liên kết với protein Gi, giúp cân bằng hiệu ứng của protein Gs đối với việc sản xuất adenozin monophosphate vòng và kích hoạt con đường tín hiệu phosphatidylinositol 3-kinase (PI3K)–Akt. Trong một số rối loạn tim mạch, bao gồm suy tim, cũng như trong quá trình lão hóa và trong các mô hình động vật gặp stress môi trường, đã quan sát thấy sự giảm tỷ lệ β1/β2-AR và kích hoạt con đường tín hiệu β2-AR-Gi-PI3K–Akt. Các nghiên cứu gần đây đã chỉ ra rằng sirtuins điều chỉnh một số quá trình sinh học nhất định, bao gồm phản ứng tế bào với stress, thông qua việc kích hoạt con đường tín hiệu PI3K–Akt và các phân tử hạ nguồn như p53, Akt, HIF1-α, và yếu tố nhân kappa B (NF-κB). Trong tim, SIRT1, SIRT3 và β2-AR đóng vai trò quan trọng trong việc điều hòa trao đổi chất năng lượng của tế bào cơ tim, stress oxy hóa, sản xuất các loài oxy phản ứng, và tự thực bào. SIRT1 và phức hợp β2-AR-Gi cũng kiểm soát các con đường tín hiệu sống sót và chết của tế bào. Tại đây, chúng tôi xem xét vai trò của β2-AR và sirtuins trong quá trình lão hóa, suy tim, và thích nghi với căng thẳng, tập trung vào mối tương tác khả thi giữa hai yếu tố này. Mối quan hệ đó, nếu được chứng minh, xứng đáng được nghiên cứu thêm trong bối cảnh chức năng và rối loạn chức năng tim.

Từ khóa

#beta-adrenergic receptors #sirtuins #heart failure #aging #stress adaptation

Tài liệu tham khảo

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