Xin Haolin, Yu Ning, Yang Qian, Zou Xuan, An Zhongping, Zhou Guanen
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Department of Neurology, Huanhu Hospital Tianjin China
RSC Adv. 2023 Jun 28;13(28):19477-19484. doi: 10.1039/d3ra02943c. eCollection 2023 Jun 22.
Pyocyanin, a secreted virulence factor, plays an essential role during infection. Infection of the central nervous system by this bacterium results in high mortality, but the studies on its mechanism are still rather limited. In this study, we first evaluate the neuronal damage caused by pyocyanin exposure in neuronal HT22 cells. Pyocyanin leads to mitochondrial syndrome and antioxidant defense disruption, therefore increasing intercellular reactive oxygen species (ROS) production. Several typical superior antioxidant polyphenols effectively protect against pyocyanin-induced neuronal cell damage. These findings suggest the neuronal protective activity more or less relies on the structure, rather than the residues. Pre-incubation of catechin activates the essential pathway, indicating inverse correlation of ERK and AMPK phosphorylation participates in this process. These data outline a novel strategy to eliminate intracellular generated ROS. The investigated candidates could be potentially used as therapeutic agents against various ROS-related neurological diseases.
绿脓菌素是一种分泌型毒力因子,在感染过程中起着至关重要的作用。这种细菌感染中枢神经系统会导致高死亡率,但对其机制的研究仍然相当有限。在本研究中,我们首先评估了绿脓菌素暴露对神经元HT22细胞造成的神经元损伤。绿脓菌素会导致线粒体综合征和抗氧化防御破坏,从而增加细胞间活性氧(ROS)的产生。几种典型的优质抗氧化多酚能有效保护细胞免受绿脓菌素诱导的神经元细胞损伤。这些发现表明,神经元保护活性或多或少依赖于结构,而非残基。儿茶素预孵育可激活关键途径,表明细胞外信号调节激酶(ERK)和腺苷酸活化蛋白激酶(AMPK)磷酸化的负相关参与了这一过程。这些数据概述了一种消除细胞内产生的ROS的新策略。所研究的候选物有可能用作治疗各种与ROS相关的神经疾病的药物。