N-acetyloxfenicine strongly induces mitohormesis in mice as well as in insects
N-acetyloxfenicine strongly induces mitohormesis in mice as well as in insects
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DOI：
10.1002/1873-3468.14566
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发表时间：
2023-01-11
期刊：
影响因子：
3.5
通讯作者：
Hayakawa, Yoichi
中科院分区：
文献类型：
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作者：
Matsumura, Takashi;Ono, Masaya;Hayakawa, Yoichi
线粒体兴奋作用定义了对轻度线粒体应激的适应性反应诱导的适应性增加。在这里，我们表明，N-乙酰氧基非尼辛（NAO）发挥更高的耐热性比内源性有丝分裂兴奋诱导剂，N-乙酰酪氨酸（NAT）。在注射奥非尼辛的粘虫幼虫中未观察到这种活性，表明N-乙酰化的重要性。NAO诱导的激素效应由线粒体的瞬时扰动触发，这引起ROS产生的小幅增加，并导致逆行反应，包括通过激活FoxO转录因子增强抗氧化酶基因的表达。此外，预处理NAO显着抑制应激诱导的脂质过氧化反应的小鼠和大肠癌HCT 116细胞移植到裸鼠的生长。总之，NAO是一种有效的有丝分裂兴奋诱导剂，在结构和功能方面与NAT相似。
Mitohormesis defines the increase in fitness induced by adaptive responses to mild mitochondrial stress. Here, we show that N-acetyloxfenicine (NAO) exerted higher thermotolerance than an endogenous mitohormesis inducer, N-acetyltyrosine (NAT). This activity was not observed in armyworm larvae injected with oxfenicine, suggesting the importance of N-acetylation. NAO-induced hormetic effect was triggered by transient perturbation of mitochondria, which causes a small increase in ROS production and leads to retrograde responses including enhanced expression of antioxidant enzyme genes via activation of FoxO transcription factors. Furthermore, pretreatment with NAO significantly repressed stress-induced peroxidation of lipids in mice and growth of colorectal cancer HCT116 cells that had been transplanted into nude mice. Taken together, NAO is a potent mitohormesis inducer that is similar to NAT in terms of structure and functions.