PMID- 31927658 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20210518 IS - 1573-6881 (Electronic) IS - 0145-479X (Linking) VI - 52 IP - 1 DP - 2020 Feb TI - The lncRNA FAL1 protects against hypoxia-reoxygenation- induced brain endothelial damages through regulating PAK1. PG - 17-25 LID - 10.1007/s10863-019-09819-2 [doi] AB - Dysregulation of cerebral microvascular endothelial cells plays an important role in the pathogenesis of stroke. However, the underlying mechanisms still need to be elucidated. In the current study, we found that the long non-coding RNA (lncRNA) FAL1 was significantly reduced in response to oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in human primary brain microvascular endothelial cells (HBMVECs). Interestingly, overexpression of FAL1 ameliorated OGD/R-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and increasing the level of reduced glutathione (GSH). Also, overexpression of FAL1 suppressed OGD/R-induced secretions of interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and high mobility group box-1 (HMGB-1). We then found that OGD/R-induced reduction of cell viability and release of lactate dehydrogenase (LDH) were prevented by overexpression of FAL1. Additionally, exposure to OGD/R significantly reduced the phosphorylated levels of PAK1 and AKT as well as the total level of proliferating cell nuclear antigen (PCNA), which was restored by overexpression of FAL1. Importantly, overexpression of FAL1 restored OGD/R-induced reduction in the expression of endothelial nitric oxide synthase (eNOS) and the subsequent release of nitric oxide (NO). Our results implicate that FAL1 might be involved in the process of brain endothelial cell damage. FAU - Gao, Mingqing AU - Gao M AD - Department of Neurosurgery, The Affiliated Hospital of Wei fang Medical University, No. 2428, Yuhe Road, Weifang, 261031, Shandong, China. FAU - Fu, Jieting AU - Fu J AD - Department of Hematology, The Affiliated Hospital of Wei fang Medical University, Shandong, China. FAU - Wang, Yanqiang AU - Wang Y AUID- ORCID: 0000-0002-6747-9162 AD - Department of Neurology, The Affiliated Hospital of Wei fang Medical University, Shandong, China. bingjieli025@yeah.net. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200111 PL - United States TA - J Bioenerg Biomembr JT - Journal of bioenergetics and biomembranes JID - 7701859 RN - 0 (RNA, Long Noncoding) RN - EC 2.7.11.1 (PAK1 protein, human) RN - EC 2.7.11.1 (p21-Activated Kinases) SB - IM MH - Brain/*physiopathology MH - Cell Hypoxia MH - Endothelial Cells/*metabolism MH - Humans MH - RNA, Long Noncoding/*metabolism MH - Signal Transduction MH - p21-Activated Kinases/*metabolism OTO - NOTNLM OT - Cerebral microvascular endothelial cells OT - FAL1 OT - Oxygen-glucose deprivation and reoxygenation OT - Stroke OT - lncRNA EDAT- 2020/01/14 06:00 MHDA- 2021/05/19 06:00 CRDT- 2020/01/14 06:00 PHST- 2019/05/28 00:00 [received] PHST- 2019/12/12 00:00 [accepted] PHST- 2020/01/14 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2020/01/14 06:00 [entrez] AID - 10.1007/s10863-019-09819-2 [pii] AID - 10.1007/s10863-019-09819-2 [doi] PST - ppublish SO - J Bioenerg Biomembr. 2020 Feb;52(1):17-25. doi: 10.1007/s10863-019-09819-2. Epub 2020 Jan 11.