Miyamoto D, Kusagaya Y, Endo N, Sometani A, Takeo S, Suzuki T, Arima Y, Nakajima K, Suzuki Y
Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Antiviral Res. 1998 Aug;39(2):89-100. doi: 10.1016/s0166-3542(98)00034-5.
The effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in Madin-Darby canine kidney (MDCK) cells were examined by DNA fragmentation and flow cytometry. Among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected MDCK cells with influenza A/PR/8/34(H1N1), A/Shingapol/1/57(H2N2), A/Aichi/2/68(H3N2) and B/Lee/40 viruses, at concentrations of more than 5 microM. These results indicate that the copper chelates inhibit influenza virus-induced apoptosis and that the inhibitory effects may be independent of influenza virus subtype or types. Furthermore, the copper chelates also inhibited the release of the viruses from the infected MDCK cells during apoptosis. The anti-apoptotic effects of the copper chelates may occur 2 4 h postinfection, suggesting that the copper chelates affect MDCK cells directly in the early stage of influenza virus-induced apoptosis. In this study, we demonstrated that thujaplicin-copper chelates inhibit influenza virus-induced apoptosis of MDCK cells and also inhibit virus replication and release from the infected cells.
通过DNA片段化和流式细胞术检测了α-、β-和γ-崖柏素及其六种金属螯合物对人甲型流感病毒诱导的马-达二氏犬肾（MDCK）细胞凋亡的影响。在所测试的化合物中，崖柏素铜螯合物在浓度高于5微摩尔时，可抑制甲型流感病毒A/PR/8/34（H1N1）、A/新加坡/1/57（H2N2）、A/爱知/2/68（H3N2）和乙型流感病毒B/李/40感染的MDCK细胞中诱导的凋亡。这些结果表明，铜螯合物可抑制流感病毒诱导的凋亡，且抑制作用可能与流感病毒亚型无关。此外，铜螯合物还抑制了凋亡过程中病毒从感染的MDCK细胞中的释放。铜螯合物的抗凋亡作用可能在感染后2至4小时出现，这表明铜螯合物在流感病毒诱导凋亡的早期直接影响MDCK细胞。在本研究中，我们证明了崖柏素-铜螯合物可抑制流感病毒诱导的MDCK细胞凋亡，还可抑制病毒复制及从感染细胞中的释放。
