Argon Mediates Anti-Apoptotic Signaling and Neuroprotection via Inhibition of Toll-Like Receptor 2 and 4

Recently, the noble gas argon attracted significant attention due to its neuroprotective properties. However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hyp...

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Veröffentlicht in:PloS one 2015-12, Vol.10 (12), p.e0143887
Hauptverfasser: Ulbrich, Felix, Kaufmann, Kai, Roesslein, Martin, Wellner, Franziska, Auwärter, Volker, Kempf, Jürgen, Loop, Torsten, Buerkle, Hartmut, Goebel, Ulrich
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container_issue 12
container_start_page e0143887
container_title PloS one
container_volume 10
creator Ulbrich, Felix
Kaufmann, Kai
Roesslein, Martin
Wellner, Franziska
Auwärter, Volker
Kempf, Jürgen
Loop, Torsten
Buerkle, Hartmut
Goebel, Ulrich
description Recently, the noble gas argon attracted significant attention due to its neuroprotective properties. However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4. Apoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells' surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis. Argon 75 Vol% treatment abolished rotenone-induced apoptosis. This effect was attenuated dose- and time-dependently. Argon treatment was accompanied with a significant reduction of TLR2 and TLR4 receptor density and protein expression. Moreover, argon mediated increase in ERK1/2 phosphorylation was attenuated after inhibition of TLR signaling. ERK1/2 and TLR signaling inhibitors abolished the anti-apoptotic and cytoprotective effects of argon. Immunohistochemistry results strengthened these findings. These findings suggest that argon-mediated anti-apoptotic and neuroprotective effects are mediated via inhibition of TLR2 and TLR4.
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However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4. Apoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells' surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis. 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However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4. Apoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells' surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis. 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subjects Anesthesiology
Apoptosis
Apoptosis - drug effects
Argon
Argon - pharmacology
Attention
Brain research
Carbon dioxide
Caspase
Caspase 3 - metabolism
Caspase-3
Cell culture
Cell cycle
Cell Line, Tumor
Cellular signal transduction
Cytometry
Extracellular signal-regulated kinase
Flow cytometry
Forensic medicine
Health aspects
Humans
Hypoxia
Immune system
Immunohistochemistry
Inhibition
Intensive care
MAP Kinase Signaling System - drug effects
Nervous system
Neuroblastoma
Neuroblastoma - drug therapy
Neuroblastoma - metabolism
Neuroprotection
Neuroprotection - drug effects
Neuroprotective Agents - pharmacology
Neurosciences
Oxygen
Phosphorylation
Phosphorylation - drug effects
Proteins
Pulmonary arteries
Rare gases
Receptor density
Receptors
Rodents
Rotenone
Rotenone - pharmacology
Signal Transduction - drug effects
Signaling
TLR2 protein
TLR4 protein
Toll-Like Receptor 2 - antagonists & inhibitors
Toll-Like Receptor 4 - antagonists & inhibitors
Toll-like receptors
Toxicology
Traumatic brain injury
title Argon Mediates Anti-Apoptotic Signaling and Neuroprotection via Inhibition of Toll-Like Receptor 2 and 4
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T02%3A44%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Argon%20Mediates%20Anti-Apoptotic%20Signaling%20and%20Neuroprotection%20via%20Inhibition%20of%20Toll-Like%20Receptor%202%20and%204&rft.jtitle=PloS%20one&rft.au=Ulbrich,%20Felix&rft.date=2015-12-01&rft.volume=10&rft.issue=12&rft.spage=e0143887&rft.pages=e0143887-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0143887&rft_dat=%3Cgale_plos_%3EA436776226%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1738477600&rft_id=info:pmid/26624894&rft_galeid=A436776226&rft_doaj_id=oai_doaj_org_article_4c52579cadc84bb0a49d62acc2c4426f&rfr_iscdi=true