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多德二甲基胺氧化物可能诱导溶解体相关的细胞死亡:潜在的脂毒性
Eun-Jung Park1, Minseok Seo2, Wonkyun Jung3
1Department of Biochemistry and Molecular Biology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Human Health and Environmental Toxins Research Center, Kyung Hee University, 02447, Republic of Korea.
概括
家庭用品中的多德二甲基胺氧化物 (DDAO) 通过破坏线粒体和改变脂质代谢,导致细胞死亡. 这表明DDAO可能通过溶酶体通路诱导脂毒性.
科学领域:
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
- 生物化学 生物化学
背景情况:
- 十二二甲基胺氧化物 (DDAO) 是家用清洁产品中常见的成分.
- 了解DDAO的细胞毒性机制对于产品安全至关重要.
研究的目的:
- 研究DDAO在人类支气管上皮细胞中的潜在毒性机制.
- 为了阐明DDAO暴露的细胞和分子效应.
主要方法:
- 暴露人类支气管上皮细胞DDAO6小时.
- 评估细胞活力,细胞阻抗,线粒体功能 (细胞染色体C,ATP生产,线粒体体积) 和细胞内成分.
- 对细胞因子和矩阵金属蛋白酶 (MMP) 水平的分析.
- 对LAMP-2蛋白表达和酸性体积的评估.
- 基因表达分析专注于脂质代谢.
主要成果:
- 暴露于DDAO降低了细胞活力,并诱导了细胞质真空形成的非亡细胞死亡.
- 观察到线粒体功能障碍,包括内膜凝结,细胞染色体C增加,ATP产生减少,线粒体体积减少.
- DDAO改变了炎症媒介的分泌,增加了IL-6,IL-11,MMP-1和MMP-3.
- 增加了LAMP-2的表达和扩大的酸性部分被注意到,在40μg/mL时迅速下降.
- 与脂质代谢相关的基因受到DDAO治疗的显著影响.
结论:
- DDAO诱导细胞死亡,可能是通过溶酶体相关的细胞死亡和脂毒性.
- 线粒体膜的结构损伤是DDAO毒性的关键机制.
- lysosomal 膜蛋白可能对DDAO诱导的细胞损伤起着保护作用.
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