Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway | Bentham Science
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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Propofol Protects Against TNF-α-induced Blood-brain Barrier Disruption via the PIM-1/eNOS/NO Pathway

Author(s): Yan Lu*, Zhendong Xu*, Fuyi Shen, Rong Lin, Haibing Li, Xiang Lv* and Zhiqiang Liu*

Volume 17, Issue 4, 2020

Page: [471 - 479] Pages: 9

DOI: 10.2174/1567202617999200819142021

Price: $65

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Abstract

Background: The Inflammatory cytokine, tumor necrosis factor-α (TNF-α), disrupts blood-brain barrier (BBB). Propofol reportedly exerts an anti-inflammatory effect in the central nervous system.

Objective: We hypothesized that propofol could provide a protective effect against TNF-α-induced disruption in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms.

Methods: The hCMEC/D3 cell monolayers were pretreated with propofol, followed by TNF-α treatment. The integrity of BBB was reflected by assessing the trans-endothelial electrical resistance (TEER) and determining the expression of proteins within tight junctions (TJs). The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit. The expression of ZO-1, claudin-5, occludin, TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), proviral-integration site for Moloney murine leukaemia virus (PIM)-1kinase, the phosphorylation of endothelial nitric oxide synthase at ser633 (peNOS-ser633) were detected by western blot.

Results: In hCMEC/D3 cells, TNF-α treatment markedly disrupted the integrity of BBB. Further, we found TNF-α treatment could increase the expression of PIM-1, then activate the phosphorylation of eNOS and induce the release of nitric oxide (NO). More importantly, we found that TNF- α-impaired BBB integrity could be reversed by propofol.

Conclusion: These results suggest that the PIM-1/eNOS/NO pathway plays a vital role, in which Propofol protects against TNF-α-induced blood-brain barrier disruption.

Keywords: Propofol, blood-brain barrier, postoperative cognitive dysfunction, TNF-α, interleukin, endothelial cells.

« Previous Next »
[1]
Skvarc DR, Berk M, Byrne LK, et al. Post-operative cognitive dysfunction: An exploration of the inflammatory hypothesis and novel therapies. Neurosci Biobehav Rev 2018; 84: 116-33.
[http://dx.doi.org/10.1016/j.neubiorev.2017.11.011] [PMID: 29180259]
[2]
Deiner S, Liu X, Lin HM, et al. Does postoperative cognitive decline result in new disability after surgery? Ann Surg 2020; [Epub ahead of print].
[http://dx.doi.org/10.1097/SLA.0000000000003764] [PMID: 32149824]
[3]
Liu Y, Yin Y. Emerging roles of immune cells in postoperative cognitive dysfunction. Mediators Inflamm 2018; 2018: 6215350
[http://dx.doi.org/10.1155/2018/6215350] [PMID: 29670465]
[4]
Wu Y, Dou J, Wan X, et al. Histone deacetylase inhibitor MS-275 alleviates postoperative cognitive dysfunction in rats by inhibiting hippocampal neuroinflammation. Neuroscience 2019; 417: 70-80.
[http://dx.doi.org/10.1016/j.neuroscience.2019.08.020] [PMID: 31430527]
[5]
Chen L, Dong R, Lu Y, et al. MicroRNA-146a protects against cognitive decline induced by surgical trauma by suppressing hippocampal neuroinflammation in mice. Brain Behav Immun 2019; 78: 188-201.
[http://dx.doi.org/10.1016/j.bbi.2019.01.020] [PMID: 30685530]
[6]
Wang B, Li S, Cao X, et al. Blood-brain barrier disruption leads to postoperative cognitive dysfunction. Curr Neurovasc Res 2017; 14(4): 359-67.
[http://dx.doi.org/10.2174/1567202614666171009105825] [PMID: 28990533]
[7]
Bian Y, Yamashita T, Taira Y, et al. Polyphenolic complex attenuates inflammatory response and blood-brain barrier disruption. Curr Neurovasc Res 2020; [Epub ahead of print].
[http://dx.doi.org/10.2174/1567202617666200517105727] [PMID: 32416676]
[8]
Hashimoto Y, Tachibana K, Kondoh M. Tight junction modulators for drug delivery to the central nervous system. Drug Discov Today 2020; 25(8): 1477-86.
[PMID: 32439607]
[9]
Matsuhisa K, Watari A, Iwamoto K, Kondoh M, Yagi K. Lignosulfonic acid attenuates NF-kappaB activation and intestinal epithelial barrier dysfunction induced by TNF-alpha/IFN-gamma in Caco-2 cells. J Nat Med 2018; 72(2): 448-55.
[PMID: 29275476]
[10]
Chang R, Yee KL, Sumbria RK. Tumor necrosis factor α Inhibition for Alzheimer’s disease. J Cent Nerv Syst Dis 2017; 9: 1179573517709278.
[http://dx.doi.org/10.1177/1179573517709278] [PMID: 28579870]
[11]
Wang F, Ji S, Wang M, et al. HMGB1 promoted P-glycoprotein at the blood-brain barrier in MCAO rats via TLR4/NF-κB signaling pathway. Eur J Pharmacol 2020; 880: 173189.
[http://dx.doi.org/10.1016/j.ejphar.2020.173189] [PMID: 32417325]
[12]
Brymer KJ, Romay-Tallon R, Allen J, Caruncho HJ, Kalynchuk LE. Exploring the potential antidepressant mechanisms of TNFα antagonists. Front Neurosci 2019; 13: 98.
[http://dx.doi.org/10.3389/fnins.2019.00098] [PMID: 30804748]
[13]
Velazquez R, Shaw DM, Caccamo A, Oddo S. Pim1 inhibition as a novel therapeutic strategy for Alzheimer’s disease. Mol Neurodegener 2016; 11(1): 52.
[http://dx.doi.org/10.1186/s13024-016-0118-z] [PMID: 27412291]
[14]
Lim R, Barker G, Lappas M. Inhibition of PIM1 kinase attenuates inflammation-induced pro-labour mediators in human foetal membranes in vitro. Mol Hum Reprod 2017; 23(6): 428-40.
[http://dx.doi.org/10.1093/molehr/gax013] [PMID: 28333279]
[15]
Chen M, Yi B, Zhu N, et al. Pim1 kinase promotes angiogenesis through phosphorylation of endothelial nitric oxide synthase at Ser-633. Cardiovasc Res 2016; 109(1): 141-50.
[http://dx.doi.org/10.1093/cvr/cvv250] [PMID: 26598507]
[16]
Garcia V, Sessa WC. Endothelial NOS: Perspective and recent developments. Br J Pharmacol 2019; 176(2): 189-96.
[http://dx.doi.org/10.1111/bph.14522] [PMID: 30341769]
[17]
Zhang H, Pan Q, Xie Z, et al. Implication of microRNA503 in brain endothelial cell function and ischemic stroke. Transl Stroke Res 2020; 11: 1148-64.
[http://dx.doi.org/10.1007/s12975-020-00794-0] [PMID: 32285355]
[18]
Sun B, Ou H, Ren F, et al. Propofol inhibited autophagy through Ca2+/CaMKKβ/AMPK/mTOR pathway in OGD/R-induced neuron injury. Mol Med 2018; 24(1): 58.
[http://dx.doi.org/10.1186/s10020-018-0054-1] [PMID: 30470173]
[19]
Li X, Yao L, Liang Q, Qu H, Cai H. Propofol protects hippocampal neurons from hypoxia-reoxygenation injury by decreasing calcineurin-induced calcium overload and activating YAP signaling. Oxid Med Cell Longev 2018; 2018: 1725191.
[http://dx.doi.org/10.1155/2018/1725191] [PMID: 30046369]
[20]
Lu Y, Gu Y, Ding X, Wang J, Chen J, Miao C. Intracellular Ca2+ homeostasis and JAK1/STAT3 pathway are involved in the protective effect of propofol on BV2 microglia against hypoxia-induced inflammation and apoptosis. PLoS One 2017; 12(5): e0178098.
[http://dx.doi.org/10.1371/journal.pone.0178098] [PMID: 28542400]
[21]
Sajja RK, Prasad S, Cucullo L. Impact of altered glycaemia on blood-brain barrier endothelium: an in vitro study using the hCMEC/D3 cell line. Fluids Barriers CNS 2014; 11(1): 8.
[http://dx.doi.org/10.1186/2045-8118-11-8] [PMID: 24708805]
[22]
Sall JW, Stratmann G, Leong J, Woodward E, Bickler PE. Propofol at clinically relevant concentrations increases neuronal differentiation but is not toxic to hippocampal neural precursor cells in vitro. Anesthesiology 2012; 117(5): 1080-90.
[http://dx.doi.org/10.1097/ALN.0b013e31826f8d86] [PMID: 23001052]
[23]
Lu Y, Chen W, Lin C, et al. The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIα/nNOS pathway. BMC Anesthesiol 2017; 17(1): 32.
[http://dx.doi.org/10.1186/s12871-017-0327-1] [PMID: 28241801]
[24]
Weksler B, Romero IA, Couraud PO. The hCMEC/D3 cell line as a model of the human blood brain barrier. Fluids Barriers CNS 2013; 10(1): 16.
[http://dx.doi.org/10.1186/2045-8118-10-16] [PMID: 23531482]
[25]
Enea M, Peixoto de Almeida M, Eaton P, et al. A multiparametric study of gold nanoparticles cytotoxicity, internalization and permeability using an in vitro model of blood-brain barrier. Influence of size, shape and capping agent. Nanotoxicology 2019; 13(7): 990-1004.
[http://dx.doi.org/10.1080/17435390.2019.1621398] [PMID: 31106633]
[26]
Aparicio-Blanco J, Romero IA, Male DK, Slowing K, García-García L, Torres-Suárez AI. Cannabidiol enhances the passage of lipid nanocapsules across the blood-brain barrier both in vitro and in vivo. Mol Pharm 2019; 16(5): 1999-2010.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b01344] [PMID: 30865462]
[27]
Greene C, Hanley N, Campbell M. Claudin-5: Gatekeeper of neurological function. Fluids Barriers CNS 2019; 16(1): 3.
[http://dx.doi.org/10.1186/s12987-019-0123-z] [PMID: 30691500]
[28]
Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE. Transmembrane proteins of the tight junctions at the blood-brain barrier: Structural and functional aspects. Semin Cell Dev Biol 2015; 38: 16-25.
[http://dx.doi.org/10.1016/j.semcdb.2014.11.004] [PMID: 25433243]
[29]
Zhang S, Dong H, Zhang X, Li N, Sun J, Qian Y. Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption Behav Brain Res 2016; 298(Pt B): 158-66.
[http://dx.doi.org/10.1016/j.bbr.2015.11.003]
[30]
Rochfort KD, Cummins PM. The blood-brain barrier endothelium: A target for pro-inflammatory cytokines. Biochem Soc Trans 2015; 43(4): 702-6.
[http://dx.doi.org/10.1042/BST20140319] [PMID: 26551716]
[31]
Xu Z, Lu Y, Wang J, Ding X, Chen J, Miao C. The protective effect of propofol against TNF-α-induced apoptosis was mediated via inhibiting iNOS/NO production and maintaining intracellular Ca2+ homeostasis in mouse hippocampal HT22 cells. Biomed Pharmacother 2017; 91: 664-72.
[http://dx.doi.org/10.1016/j.biopha.2017.04.110] [PMID: 28499237]
[32]
Schwartz M, Deczkowska A. Neurological disease as a failure of brain-immune crosstalk: The multiple faces of neuroinflammation. Trends Immunol 2016; 37(10): 668-79.
[http://dx.doi.org/10.1016/j.it.2016.08.001] [PMID: 27616557]
[33]
Yu S, Xin W, Jiang Q, Li A. 2020. Propofol exerts neuroprotective functions by down-regulating microRNA-19a in glutamic acid-induced PC12 cells. Biofactors 2020; [Epub ahead of print].
[http://dx.doi.org/10.1002/biof.1607] [PMID: 31913544]
[34]
Zhang HB, Tu XK, Chen Q, Shi SS. Propofol reduces inflammatory brain injury after subarachnoid hemorrhage: Involvement of PI3K/Akt pathway. J Stroke Cerebrovasc Dis 2019; 28(12): 104375.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.104375] [PMID: 31590996]
[35]
Wang C, Wei Y, Yuan Y, et al. The role of PI3K-mediated AMPA receptor changes in post-conditioning of propofol in brain protection. BMC Neurosci 2019; 20(1): 51.
[http://dx.doi.org/10.1186/s12868-019-0532-6] [PMID: 31570094]
[36]
Roh GU, Song Y, Park J, Ki YM, Han DW. Effects of propofol on the inflammatory response during robot-assisted laparoscopic radical prostatectomy: A prospective randomized controlled study. Sci Rep 2019; 9(1): 5242.
[http://dx.doi.org/10.1038/s41598-019-41708-x] [PMID: 30918320]
[37]
Asati V, Mahapatra DK, Bharti SK. PIM kinase inhibitors: Structural and pharmacological perspectives. Eur J Med Chem 2019; 172: 95-108.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.050] [PMID: 30954777]
[38]
Siragusa M, Fleming I. The eNOS signalosome and its link to endothelial dysfunction. Pflugers Arch 2016; 468(7): 1125-37.
[http://dx.doi.org/10.1007/s00424-016-1839-0] [PMID: 27184745]
[39]
Xuan FL, Wang HW, Cao LX, et al. Propofol inhibits cerebellar parallel fiber-purkinje cell synaptic transmission via activation of presynaptic GABAB receptors in vitro in mice. Front Neurosci 2018; 12: 922.
[http://dx.doi.org/10.3389/fnins.2018.00922] [PMID: 30574067]
[40]
Ren L, Hao X, Min S, et al. Anesthetics alleviate learning and memory impairment induced by electroconvulsive shock by regulation of NMDA receptor-mediated metaplasticity in depressive rats. Neurobiol Learn Mem 2018; 155: 65-77.
[http://dx.doi.org/10.1016/j.nlm.2018.06.013] [PMID: 29953948]

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