PRMT6-FOXO3A通过调整肠道缺血-再输液损伤中帕金表达的表达来减轻亡
Xinwan Wu1, Yu Zhou, Hongjiao Xu
1Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shock (Augusta, Ga.)
|February 7, 2024
概括
蛋白质氨酸甲基转移酶6 (PRMT6) 通过通过FoxO3a甲基化上调帕金表达,从而降低细胞亡,从而防止肠道缺血-再输液损伤 (IIRI).
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 肠道缺血-再输损伤 (IIRI) 是一种严重的疾病,具有显著的发病率和死亡率.
- 了解IIRI背后的分子机制对于开发有效的治疗策略至关重要.
研究的目的:
- 在IIRI中调查蛋白质氨酸甲基转移酶6 (PRMT6) ,叉头盒O3a (FoxO3a) 和帕金的作用.
- 阐明涉及PRMT6,FoxO3a和Parkins在IIRI期间调解细胞亡的调节途径.
主要方法:
- 已建立的IIRI和氧-葡萄糖剥夺/再输液 (OGD/R) 细胞模型.
- 使用过度基因表达/敲击,西部污染和亡分析 (酸,TUNEL,流细胞计).
- 通过血素和氨酸染色确认了IIRI模型,并评估了蛋白质表达水平.
主要成果:
- IIRI和OGD/R增加了亡标志物 (Bax) 和减少了抗亡标志物 (Bcl-2).
- 帕金过度表达减少了OGD/R损伤;PRMT6调节了FoxO3a甲基化,直接结合帕金.
- 过度表达PRMT6减弱了OGD/R诱导的帕金斯降低调节和亡,而PRMT6倒退则加剧了它. 在IIRI小鼠中,PRMT6,FoxO3a和帕金的水平下降.
结论:
- 通过调节 FoxO3a 甲基化,PRMT6 提高了帕金表达的调节.
- 这种PRMT6-FoxO3a-Parkin轴通过减少肠上皮细胞亡,对IIRI起着保护作用.
- 准PRMT6可能为IIRI提供治疗方法.
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