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CircRNA_0001449 disturbs phosphatidylinositol homeostasis and AKT activity by enhancing Osbpl5 translation in transient cerebral ischemia
Redox Biology ( IF 10.7 ) Pub Date : 2020-02-10 , DOI: 10.1016/j.redox.2020.101459
Fei-Fei Shang 1 , Li Luo 1 , Jianghong Yan 1 , Qiubo Yu 1 , Yongzheng Guo 2 , Yuchen Wen 1 , Xiao-Li Min 3 , Ling Jiang 4 , Xiang He 5 , Wei Liu 6
Affiliation  

Phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] is a phosphorylated derivative of phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], which recruit and activate AKT in the plasma membrane (PM) to promote cellular survival. ORP5 anchors at the endoplasmic reticulum (ER)-PM contact sites and acts as a PI(4)P and PI(4,5)P2/phosphatidylserine (PS) exchanger. Here, a lipidomics analysis of the sensorimotor cortex revealed that transient middle cerebral artery occlusion (tMCAO) disturbs the homeostasis of phosphatidylinositols (PIs) and PS between the PM and ER. Conditional knockout mice showed that ORP5 contributes to this abnormal distribution. Abolishing the ORP5 gene significantly inhibited apoptosis and autophagy. RNA sequencing and RNA pull down analyses confirmed a competing endogenous RNA pathway in which circ_0001449 sponges miR-124-3p and miR-32-5p to promote translation. Our data showed that circRNA_0001449 regulates membrane homeostasis via ORP5 and is involved in the AKT survival pathway.

中文翻译:


CircRNA_0001449 通过增强短暂性脑缺血中的 Osbpl5 翻译来扰乱磷脂酰肌醇稳态和 ​​AKT 活性



磷脂酰肌醇-3,4,5-三磷酸 [PI(3,4,5)P3] 是磷脂酰肌醇 4-磷酸 [PI(4)P] 和磷脂酰肌醇 4,5-二磷酸 [PI(4,5)] 的磷酸化衍生物P2],募集并激活质膜 (PM) 中的 AKT 以促进细胞存活。 ORP5 锚定在内质网 (ER)-PM 接触位点并充当 PI(4)P 和 PI(4,5)P2/磷脂酰丝氨酸 (PS) 交换器。在这里,感觉运动皮层的脂质组学分析表明,短暂的大脑中动脉闭塞 (tMCAO) 扰乱了 PM 和 ER 之间磷脂酰肌醇 (PI) 和 PS 的稳态。条件性基因敲除小鼠表明 ORP5 导致了这种异常分布。消除ORP5基因可显着抑制细胞凋亡和自噬。 RNA测序和RNA pull down分析证实了一条竞争性内源RNA途径,其中circ_0001449海绵miR-124-3p和miR-32-5p以促进翻译。我们的数据表明,circRNA_0001449 通过 ORP5 调节膜稳态,并参与 AKT 生存途径。
更新日期:2020-02-10
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