Gymnodimine-A (GYM-A)是一种由某些海洋甲藻产生的环状伊米因类生物毒素。它通过腹腔注射能够导致小鼠迅速死亡，并且在贝类中积累，有可能对人类健康构成威胁。本研究使用四种不同细胞系来评估GYM-A的生物活力。结果显示，GYM-A对每个细胞类型都具有浓度依赖性的细胞毒性，平均IC50值范围为1.39至2.79μmol/L。结果表明，细胞活力的丧失是由于4T1和Caco-2细胞的凋亡。此外，观察到GYM-A处理的细胞中线粒体膜电位的降低和半胱天冬氨酸蛋白酶的激活。在暴露于2μmol/L GYM-A的4T1和Caco-2细胞中，反应性氧化物种（ROS）和脂质过氧化物（LPO）水平显著增加，其中4T1细胞的氧化应激更为明显。此外，GYM-A处理的细胞还出现了线粒体和线粒体自噬囊的异常超微结构损伤。这些结果表明，ROS介导的线粒体途径参与了GYM-A引起的细胞毒性效应中的凋亡和线粒体自噬。这是第一次通过凋亡和氧化应激来探究GYM-A的细胞毒性机制的报告，该研究为GYM-A的潜在治疗应用提供了理论基础。版权所有 © 2023。Elsevier B.V.出版。 (Note: The translation assumes that "Elsevier B.V." does not need to be translated as it is a well-known publishing company.)

Gymnodimine-A (GYM-A) is a cyclic imine phycotoxin produced by some marine dinoflagellates. It can cause rapid death of mice via intraperitoneal administration and frequently accumulate in shellfish potentially threatening human health. In this study, four different cell lines were exposed to GYM-A for the viability assessment. Results showed that GYM-A was cytotoxic with concentration-dependent pattern to each cell type, with mean IC50 values ranging from 1.39 to 2.79 μmol L-1. Results suggested that the loss of cell viability was attributed to the apoptosis of 4T1 and Caco-2 cells. Furthermore, the collapse of mitochondrial membrane potential and caspases activation were observed in the GYM-A-treated cells. Reactive oxygen species (ROS) and lipid peroxides (LPO) levels were markedly increased in 4T1 and Caco-2 cells exposed to GYM-A at 2 μmol L-1, and the oxidative stress in 4T1 cells was more obvious than that in Caco-2 cells. Additionally, unusual ultrastructure impairment on mitochondria and mitophagosomes occurred in the GYM-A-treated cells. These results suggested that an ROS-mediated mitochondrial pathway for apoptosis and mitophagy was implicated in the cytotoxic effects induced by GYM-A. This is the first report to explore the cytotoxic mechanisms of GYM-A through apoptosis and oxidative stress, and it will provide theoretical foundations for the potential therapeutic applications of GYM-A.Copyright © 2023. Published by Elsevier B.V.