1. Toxic dinoflagellate Karenia mikimotoi induces apoptosis in Neuro-2a cells through an oxidative stress-mediated mitochondrial pathway.
- Author
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Lu, Jinfang, Niu, Xiaoqin, Wang, Hong, Zhang, He, and Guan, Wanchun
- Subjects
P53 antioncogene ,MITOCHONDRIA ,APOPTOSIS ,REACTIVE oxygen species ,OXIDATIVE stress ,MEMBRANE potential - Abstract
The dinoflagellate Karenia mikimotoi is a toxic bloom-forming species that threatens aquaculture and public health worldwide. Previous studies showed that K. mikimotoi induces neurotoxicity; however, the underlying mechanism is poorly understood. In this study, three neural cell lines were used to investigate the potential neurotoxicity of K. mikimotoi. The tested cells were exposed to a ruptured cell solution (RCS) of K. mikimotoi at different concentrations (0.5 × 10
5 , 1.0 × 105 , 2.0 × 105 , 4.0 × 105 , and 6 × 105 cells mL−1 ) for 24 h, and the RCS decreased cell viabilities and promoted Neuro-2a (N2A) cell apoptosis in a dose-dependent manner. The underlying mechanism was further investigated in N2A cells. At the biochemical level, the RCS stimulated reactive oxygen species (ROS) and malondialdehyde (MDA) formation, decreased SOD activity, and reduced mitochondrial membrane potential (MMP). At the gene level, the moderate RCS treatment (2.0 × 105 cells mL−1 ) upregulated antioxidant response genes (e.g., nrf -2, HO -1, NQO -1, and cat) to alleviate RCS-induced oxidative stress, while the high RCS treatment (4.0 × 105 cells mL−1 ) downregulated these genes, thereby aggravating oxidative stress. Meanwhile, apoptosis-related genes (e.g., p53 , caspase 3 , and bax2) were significantly upregulated and the anti-apoptotic gene bcl2 was suppressed after RCS treatment. Western blotting results for Caspase 3, Bax2 and Bcl2 were consistent with the mRNA trends. These results revealed that K. mikimotoi RCS can induce neural cell apoptosis via the oxidative stress-mediated mitochondrial pathway, providing novel insights into the neurotoxicity of K. mikimotoi. [Display omitted] • K. mikimotoi RCS shows toxicity to neural cells. • K. mikimotoi RCS induces oxidative stress and mitochondrial dysfunction in Neuro-2a cells. • K. mikimotoi RCS promotes apoptosis in Neuro-2a cells via a mitochondrial-dependent pathway. [ABSTRACT FROM AUTHOR]- Published
- 2023
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