Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China.
Department of Pharmacy, Jiujiang Traditional Chinese Medicine Hospital, Jiujiang 332900, China.
Oxid Med Cell Longev. 2022 Jul 16;2022:4135752. doi: 10.1155/2022/4135752. eCollection 2022.
Iron overload can induce reactive oxygen species (ROS) burst and liver damage. Taurine can reduce ROS production and ameliorate liver injury caused by iron overload; however, the underlying molecular mechanism remains elusive. Herein, L02 cells treated with 120 M iron dextran for 48 h showed marked oxidative stress damage and significantly increased apoptosis. Taurine protected hepatocytes by stabilizing mitochondrial membranes and resisting oxidative stress damage caused by iron overload. However, transfection with siRNA Bcl-2 virus abrogated the observed protective effects. Following treatment with taurine, B cell lymphoma-2 (Bcl-2) could inhibit the opening of the mitochondrial permeability transition pore (mPTP), subsequently stabilizing the mitochondrial membrane potential by interacting with voltage-dependent anion channel 1 (VDAC1) of mPTP. The present study is the first to clarify the mechanism underlying taurine-afforded hepatocyte protection against iron overload-induced oxidative stress via Bcl-2-mediated inhibition of mPTP opening and the antiapoptotic pathway.
铁过载可诱导活性氧（ROS）爆发和肝损伤。牛磺酸可减少 ROS 的产生，并改善铁过载引起的肝损伤；然而，其潜在的分子机制尚不清楚。在此，用 120μM 右旋糖酐铁处理 48h 的 L02 细胞表现出明显的氧化应激损伤，细胞凋亡显著增加。牛磺酸通过稳定线粒体膜和抵抗铁过载引起的氧化应激损伤来保护肝细胞。然而，用 siRNA Bcl-2 病毒转染后，观察到的保护作用被消除。用牛磺酸处理后，B 细胞淋巴瘤-2（Bcl-2）可抑制线粒体通透性转换孔（mPTP）的开放，随后通过与 mPTP 的电压依赖性阴离子通道 1（VDAC1）相互作用稳定线粒体膜电位。本研究首次阐明了牛磺酸通过 Bcl-2 介导的抑制 mPTP 开放和抗凋亡途径，为铁过载诱导的氧化应激提供肝细胞保护作用的机制。
