Valério Elisabete, Vilares Arminda, Campos Alexandre, Pereira Paulo, Vasconcelos Vitor
Unidade de Água e Solo, Departamento de Saúde Ambiental, Instituto Nacional de Saúde Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal.
Unidade de Diagnóstico Laboratorial e Referência, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Dr. Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
Toxicon. 2014 Nov;90:191-8. doi: 10.1016/j.toxicon.2014.08.059. Epub 2014 Aug 23.
Microcystins (MC) are cyanotoxins occurring globally, known for causing acute hepatotoxicity in humans/animals, tumor promotion in animals and potential carcinogenicity. The mechanism of MC toxicity is considered a multi-pathway process involving the inhibition of protein phosphatases PP1/PP2A and the production of reactive oxygen species (ROS). However, their mechanism of action is not fully characterized, thus hampering the complete hazard identification. In this study, we evaluated the effect of several microcystin-LR concentrations on the growth, ROS levels, antioxidant system response and apoptosis induction on Saccharomyces cerevisiae. Our results showed that the growth of S. cerevisiae was not inhibited when compared to control cells. However, the staining of cells with DHR123 and DHE revealed an intracellular increase of the ROS levels. This ROS increase resulted in an augment of catalase activity and inhibition of SOD. All these facts suggest that hydrogen peroxide was the main ROS induced by MCLR. Signs of apoptosis were also detected in the cells exposed to toxin. Our results show that S. cerevisiae VL3 displays MCLR toxicity effects known to occur in higher eukaryotes and confirmed that it can be a simple and good model to help further in the elucidation of MCLR molecular mechanisms of toxicity.
微囊藻毒素(MC)是一种全球范围内存在的蓝藻毒素,以可导致人类/动物急性肝毒性、促进动物肿瘤生长以及具有潜在致癌性而闻名。微囊藻毒素的毒性机制被认为是一个多途径过程,涉及对蛋白磷酸酶PP1/PP2A的抑制以及活性氧(ROS)的产生。然而,它们的作用机制尚未完全明确,从而阻碍了对其完整危害的识别。在本研究中,我们评估了几种微囊藻毒素-LR浓度对酿酒酵母的生长、ROS水平、抗氧化系统反应以及凋亡诱导的影响。我们的结果表明,与对照细胞相比,酿酒酵母的生长未受到抑制。然而,用DHR123和DHE对细胞进行染色显示细胞内ROS水平升高。这种ROS的增加导致过氧化氢酶活性增强和超氧化物歧化酶受到抑制。所有这些事实表明,过氧化氢是微囊藻毒素-LR诱导产生的主要ROS。在接触毒素的细胞中也检测到了凋亡迹象。我们的结果表明,酿酒酵母VL3表现出已知在高等真核生物中出现的微囊藻毒素-LR毒性效应,并证实它可以作为一个简单且良好的模型,有助于进一步阐明微囊藻毒素-LR的分子毒性机制。