期刊
REDOX BIOLOGY
卷 34, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2020.101459
关键词
Cerebral ischemia; Lipids and lipoprotein metabolism; Non-coding RNA; AKT
资金
- National Natural Science Foundation for Young Scientists of China [81601058]
- Basic Research and Frontier Science Exploration Foundation of Yuzhong District, Chongqing, China [20180106]
- National Natural Science Foundation of China [81860234, 81960219]
- Science and Technology Foundation of Guizhou Health and Family Planning Commission, Guizhou, China [gzwjkj2018-1-018]
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 signi ficantly inhibited apoptosis and autophagy. RNA sequencing and RNA pull down analyses con firmed a competing endogenous RNA pathway in which circ_0001449 sponges miR-124-3p and miR-32-5p to promote Osbpl5 translation. Our data showed that circRNA_0001449 regulates membrane homeostasis via ORP5 and is involved in the AKT survival pathway.
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