Prostaglandin E1 Improves Cerebral Microcirculation Through Activation of Endothelial NOS and GRPCH1
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Prostaglandin E1 Improves Cerebral Microcirculation Through Activation of Endothelial NOS and GRPCH1 Lei Liu 1 & Hexi Zhang 1 & Yijun Shi 1 & Lijian Pan 1 Received: 13 March 2020 / Accepted: 21 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Endothelial dysfunction greatly contributes to microcirculation disorder. The role of prostaglandin E1 (PGE1) in cerebral microcirculation was explored in vitro. LPS (0.5 or 1 μg/ml) was added to induce injury in human brain microvascular endothelial cells (HCMEC/D3). CCK-8 was applied to check viabilities of HCMEC/D3 before and after LPS treatment. Western blot witnessed the changes in protein expressions of inflammatory cytokines, IL-6 and TNF-α. Caspase-3/7 activity was analyzed and so were the protein expressions of pro-apoptotic gene BAX and anti-apoptotic gene Bcl-2. mRNA expressions of eNOS and GTPCH1 were evaluated by RT-qPCR. After overexpressing eNOS or GTPCH1 in LPS-induced HCMEC/D3 cells, viabilities, inflammatory cytokines, caspase-3/7 activity, and apoptosis-related genes were detected. The modulation of PGE1 in eNOS and GTPCH1 production, viability, inflammation, and apoptosis was investigated. The inhibitor of eNOS or GTPCH1 was introduced to examine impacts of eNOS or GTPCH1 could have on the PGE1 function. LPS decreased cell viabilities, eNOS and GTPCH1 expression, and promoted inflammation and apoptosis in HCMEC/D3 cells. Overexpressed eNOS or GTPCH1 promoted cell viabilities and suppressed inflammation and apoptosis. PGE1 enhanced viability and decreased inflammation and apoptosis in cells treated by LPS. PGE1 activated eNOS and GTPCH1 and inhibition of eNOS or GTPCH1 led to the attenuation of the protective functions of PGE1 in LPS-induced cells. PGE1 protected HCMEC/D3 cells from injuries induced by LPS by activation of eNOS and GTPCH1, suggesting that PGE1 might be used to help maintain cerebral microcirculation in future. Keywords PGE1 . Microcirculation . HCMEC/D3 . Apoptosis . Inflammation . eNOS . GTPCH1
Introduction Disturbances in cerebral microcirculation can lead to the occurrence of cerebral infarction, dementia, etc. (Adams 1989; Hariharan et al. 2019). Blood-brain barrier (BBB) is a key part of cerebral microcirculation, which is consisted of vascular endothelial cells, tight junctions, basilar membranes, and astrocyte foot processes (Ritter et al. 2008). Previously, dysfunction of cerebrovascular endothelial cells has been observed to elicit the disorder in cerebral microcirculation through
This study was supported by Jinshan Health Commission (JSKJ-KTQN2016-03). * Lijian Pan [email protected] 1
Department of Cardiology, Jinshan Hospital of Fudan University, No.1508, Longhang Road, Shanghai 201508, China
disturbing cerebral blood flow, BBB, and inducing inflammation in brain (Terpolilli et al. 2015). LPS is usually used to induce injury in cells or in vivo. To be specific, LPS could be utilized to induce rat brain endothelial cells to mimic dysfunction in microvascular endothelial barrier (Xiaolu et al.
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