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Prostaglandin E1 Improves Cerebral Microcirculation Through Activation of Endothelial NOS and GRPCH1

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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.

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Data Availability Statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Funding

This study was supported by Jinshan Health Commission (JSKJ-KTQN-2016-03).

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Authors and Affiliations

  1. Department of Cardiology, Jinshan Hospital of Fudan University, No.1508, Longhang Road, Shanghai, 201508, China

    Lei Liu, Hexi Zhang, Yijun Shi & Lijian Pan

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  1. Lei Liu
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  2. Hexi Zhang
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  3. Yijun Shi
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  4. Lijian Pan
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Correspondence to Lijian Pan.

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This study was supported by Jinshan Health Commission (JSKJ-KTQN-2016-03).

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Liu, L., Zhang, H., Shi, Y. et al. Prostaglandin E1 Improves Cerebral Microcirculation Through Activation of Endothelial NOS and GRPCH1. J Mol Neurosci 70, 2041–2048 (2020). https://doi.org/10.1007/s12031-020-01610-y

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  • DOI: https://doi.org/10.1007/s12031-020-01610-y

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