Alpha-thujone, widely used in beverages (1–5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-deficient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused significant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-deficient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any significant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarified in the unicellular model, S. pombe.

中文翻译：

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Pca1参与裂变酵母（裂殖酵母）中α-thujone诱导的ROS介导的凋亡细胞死亡。

已知广泛用于饮料（1-5 mg / kg）中的α-丁酮具有细胞毒性作用，但应阐明其作用方式和潜在的凋亡蛋白在酵母细胞死亡中的作用。在这项研究中，我们使用了Schizosaccharomyces pombe（一种在机制毒理学和细胞生物学中很有前途的单细胞模型生物）来研究促凋亡因子在α-thujone诱导的细胞死亡中的参与。我们显示了α-thujone诱导的ROS积累依赖性细胞毒性和凋亡。此外，我们使用了超氧化物歧化酶缺陷细胞（sod1和sod2突变体）来了解氧化应激的作用。α-thujone引起明显的细胞毒性和凋亡细胞死亡，特别是在草皮中突变体。此外，调查了两个潜在的凋亡因子pca1和pnu1（pombe caspase-1和pombe nuc1），以了解哪个因子介导了α-thujone诱导的细胞死亡。PCA1缺陷细胞显示增加的存活率和而化学治疗后，相较于亲本细胞凋亡减少pnu1突变没有引起任何显着变化，并且发现应答与亲代细胞相同。酵母以胱天蛋白酶依赖性方式响应α-丁酮，这与乙酸非常相似。总之，在单细胞模型S. pombe中阐明了由ROS介导并由Pca1驱动的α-thujone诱导的凋亡和计数机制。