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介导的透性过渡的抑制孔隙缓解帕尔米诱导的线粒体功能障碍和脂毒性

Natalia V Belosludtseva^1,2, Anna I Ilzorkina^1,2, Dmitriy A Serov^3,4

¹Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, Russia.

|September 28, 2024

概括

在脂肪酸过载时,阻断线粒体透性过渡孔,用克里克酸保护内皮细胞免受损伤. 激活孔隙会恶化线粒体功能障碍和细胞死亡.

科学领域:

生物化学生化学
细胞生物学细胞生物学
代谢障碍代谢障碍代谢障碍

背景情况:

超脂血是糖尿病等代谢障碍中血管病变的关键危险因素.
线粒体功能障碍,涉及透性过渡孔口开放,膜潜力下降和ROS过度产生,是超脂血症的病原体的核心.

研究的目的:

为了研究线粒体透性过渡 (MPT) 孔在帕尔米酸诱导的内皮细胞脂毒性中的作用.
在细胞培养模型中评估MPT孔隙调节剂 (bongkrekic acid和carboxyatractyloside) 对线粒体功能障碍的影响.

主要方法:

主要小鼠肺内皮细胞和HEK293T细胞暴露于高水平的棕酸 (0.75毫米棕酸/BSA).
线粒体功能障碍的评估是通过测量细胞活力,膜潜力,ROS产量和 lysosomal colocalization 来评估的.
研究了邦克雷克酸 (MPT孔隙阻塞剂) 和酸 (MPT孔隙激活剂) 的作用. 还进行了对ANT2的基因沉默.

主要成果:

棕酸治疗显著降低了内皮细胞活力,诱导了线粒体脱极化,并增加了ROS的产生.
邦克雷克酸保护细胞免受棕酸诱导的脂毒性和线粒体损伤.
碳盒甲酸加剧了细胞死亡,ANT2基因沉默模仿了其有害影响.

结论:

向腺核酸转位器 (ANT) 抑制MPT孔隙开放可能是一种治疗策略.
在脂肪酸过载模型中,抑制ANT可以缓解线粒体功能障碍和细胞死亡.
这些发现凸显了MPT毛孔动态在高脂血细胞损伤中的关键作用.

关键词:

在MPT中,孔径为MPT.乙酸转位器是什么?邦克雷克酸是什么意思邦克雷克酸炭酸和酸的结合物脂肪毒性脂肪毒性线粒体中的线粒体.氧化应激是一种氧化应激.棕酸盐是一种棕酸盐.

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