| 摘要: | EB 病毒為人類皰疹病毒，與許多惡性腫瘤有關，如巴克氏淋巴瘤 (Burkitt’s lymphoma)，霍奇金氏病 (Hokgkin’s disease) 及鼻咽癌 (Nasopharyngeal carcinoma) 等。之前實驗室研究發現白藜蘆醇 (Resveratrol) 具有抑制 EB 病毒溶裂蛋白質的產生，進而抑制 EB 病毒走向溶裂循環。本研究目的探討白藜蘆醇抑制 EB 病毒溶裂循環的機制探討。結果顯示白藜蘆醇在不具細胞毒性濃度能顯著抑制 SB 所誘導的 BZLF1 及 BRLF1 基因的轉錄、EB 病毒溶裂蛋白質 Rta、Zta 及 EA-D 表現量及 EB 病毒 DNA複製。也影響 sirtuin 1 mRNA 的表現量及去乙醯酶活性。細胞內 p-IκBα 與 IκBα 的比值及細胞核內 NF-κB 的表現量降低。此外，白藜蘆醇也降低 SB 所誘導 ERK 磷酸化。就本研究實驗結果推論白藜蘆醇抑制 EB 病毒溶裂循環的可能路徑：一、白藜蘆醇藉由活化 P3HR1 細胞內 sirtuin 1 基因表現，而增加去乙醯酶活性，進而抑制 NF-κB 活性，影響 EB 病毒複製。二、白藜蘆醇藉由降低細胞內 ROS 的表現量，導致 ERK 磷酸化下降，以致無法活化 BZLF1 基因轉錄，而抑制 EB 病毒的溶裂循環。三、白藜蘆醇經由降低 IκBα 的磷酸化，使 IκBα 與 NF-κB 結合，阻擋 NF-κB 進入細胞核，而使得 EB 病毒溶裂循環受到抑制。四、白藜蘆醇直接降低 ERK 的磷酸化，抑制了 EB 病毒溶裂循環。
Epstein-Barr virus (EBV) is a human herpesvirus and associated with malignant tumor, such as Burkitt’s lymphoma, Hokgkin’s disease and Nasopharyngeal carcinoma. Our earlier study found that resveratrol inhibits the expression of EB virus lytic proteins , and prevent the virus from entering lytic productive cycle investigates how. This investipation finds that resveratrol at non-cytotoxic concentrations inhibits the transcription of two EBV immediate early genes, BZLF1 and BRLF1, the expression of EBV lytic proteins, Rta, Zta and EA-D, and EBV DNA replication induced by sodium butyrate. Meanwhile, the expression of sirtuin 1 mRNA and deacetylase activity is increases by resveratrol. Intracelluar phospho-IκBα/IκBαratio and the expression of nuclear NF-κB are reduced. In addition, resveratrol reduceds ERK phosphorylation induced by sodium butyrate, suggesting the signaling pathways that are invovled in the inhibition of the EBV lytic cycle by resveratrol. This study concludes that resveratrol affects EBV DNA replication through activating of sirtuin 1 and increasing the deacetylase activity, thereby inhibiting NF-κB activity. Resveratrol via reducing the expression of intracellular ROS, decreases the phosphorylation of ERK, which is important to EBV lytic activation. Resveratrol reduces the phosphorylation of IκBα, and therefore enhances IκBα and NF-κB binding, preventing NF-κB from entering the nucleus, to activate the EB virus lytic cycle. Resveratrol directly reduces ERK phosphorylation, inhibiting the EB virus lytic cycle. |
