Lee Ju Yeun, Yoon Sei Mee, Choi Eun Ju, Lee Jinu
College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea.
College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea; Department of Integrated OMICS for Biomedical Sciences, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea.
Toxicol Appl Pharmacol. 2016 Sep 15;307:102-107. doi: 10.1016/j.taap.2016.07.022. Epub 2016 Jul 31.
Terbinafine is an antifungal agent that selectively inhibits fungal sterol synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine on gap junctional intercellular communication (GJIC). Fluorescence recovery after photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells. Treatment with terbinafine did not affect Cx43 phosphorylation status or intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC blockers. While a structurally related chemical, naftifine, attenuated GJIC, epigallocatechin gallate, another potent squalene epoxidase inhibitor with a different structure, did not. These results suggest that terbinafine inhibits GJIC with a so far unknown mechanism of action.
特比萘芬是一种抗真菌剂，它通过阻断角鲨烯环氧酶来选择性抑制真菌甾醇合成。我们评估了特比萘芬对间隙连接细胞间通讯（GJIC）的影响。光漂白后荧光恢复（FRAP）和I-YFP GJIC分析表明，特比萘芬在FRT-Cx43和LN215细胞中以可逆且剂量依赖性的方式抑制GJIC。用特比萘芬处理不影响Cx43磷酸化状态或细胞内Ca(2+)浓度，而这是各种GJIC阻滞剂的众所周知的作用机制。虽然结构相关的化学物质萘替芬会减弱GJIC，但表没食子儿茶素没食子酸酯，另一种结构不同的强效角鲨烯环氧酶抑制剂，则不会。这些结果表明，特比萘芬通过一种迄今未知的作用机制抑制GJIC。
