寇米定诱导嗜热四膜虫氧化应激、细胞凋亡及 DNA 损伤。
Induction of oxidative stress, apoptosis and DNA damage by koumine in Tetrahymena thermophila.
机构信息
Healthy Aquaculture Laboratory, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China.
Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China.
出版信息
PLoS One. 2019 Feb 12;14(2):e0212231. doi: 10.1371/journal.pone.0212231. eCollection 2019.
Koumine is a component of the Chinese medicinal herb Gelsemium elegans and is toxic to vertebrates. We used the ciliate Tetrahymena thermophila as a model to evaluate the toxic effects of this indole alkaloid in eukaryotic microorganisms. Koumine inhibited T. thermophila growth and viability in a dose-dependent manner. Moreover, this drug produced oxidative stress in T. thermophila cells and expressions of antioxidant enzymes were significantly elevated at high koumine levels (p < 0.05). Koumine also caused significant levels of apoptosis (p < 0.05) and induced DNA damage in a dose-dependent manner. Mitophagic vacuoles were present in cells indicating induction of autophagy by this drug. Expression of ATG7, MTT2/4, CYP1 and HSP70 as well as the MAP kinase pathway gene MPK1 and MPK3 were significantly altered after exposed to koumine. This study represents a preliminary toxicological evaluation of koumine in the single celled eukaryote T. thermophila.
钩吻是中国草药钩吻中的一种成分，对脊椎动物有毒。我们使用纤毛虫嗜热四膜虫作为模型，来评估这种吲哚生物碱在真核微生物中的毒性作用。钩吻以剂量依赖的方式抑制嗜热四膜虫的生长和活力。此外，这种药物在嗜热四膜虫细胞中产生氧化应激，并且在高钩吻水平下抗氧化酶的表达显著升高（p < 0.05）。钩吻还导致显著水平的细胞凋亡（p < 0.05），并以剂量依赖的方式诱导 DNA 损伤。细胞中存在噬酸性空泡，表明该药物诱导了自噬。暴露于钩吻后，ATG7、MTT2/4、CYP1 和 HSP70 的表达以及 MAP 激酶途径基因 MPK1 和 MPK3 均发生显著改变。本研究代表了对单细胞真核生物嗜热四膜虫中钩吻的初步毒理学评估。
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