Argon mediates anti-apoptotic signaling and neuroprotection via inhibition of toll-like receptor 2 and 4
Abstract: PurposeRecently, 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.MethodsApoptosis 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.ResultsArgon 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
- Standort
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                Deutsche Nationalbibliothek Frankfurt am Main
 
- Umfang
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                Online-Ressource
 
- Sprache
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                Englisch
 
- Anmerkungen
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                PLoS ONE. 10, 12 (2015), e0143887, DOI 10.1371/journal.pone.0143887, issn: 1932-6205
IN COPYRIGHT http://rightsstatements.org/page/InC/1.0 rs
 
- Schlagwort
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                Apoptosis
Immunologie
Immunsystem
Lymphozyt
Leukozyt
Immunität
Resistenz
Immunchemie
 
- Ereignis
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                Veröffentlichung
 
- (wo)
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                Freiburg
 
- (wer)
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                Universität
 
- (wann)
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                2015
 
- Urheber
 
- Beteiligte Personen und Organisationen
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                Institut für Rechtsmedizin
Klinik für Anästhesiologie und Intensivmedizin
Medizinische Fakultät
Albert-Ludwigs-Universität Freiburg
 
- DOI
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                        10.1371/journal.pone.0143887
 
- URN
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                        urn:nbn:de:bsz:25-freidok-121086
 
- Rechteinformation
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- Letzte Aktualisierung
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                        14.08.2025, 10:59 MESZ
 
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Beteiligte
- Ulbrich, Felix
 - Kaufmann, Kai Björn
 - Rösslein, Martin
 - Wellner, Franziska Marie
 - Auwärter, Volker
 - Kempf, Jürgen
 - Loop, Torsten
 - Bürkle, Hartmut
 - Göbel, Ulrich
 - Institut für Rechtsmedizin
 - Klinik für Anästhesiologie und Intensivmedizin
 - Medizinische Fakultät
 - Albert-Ludwigs-Universität Freiburg
 - Universität
 
Entstanden
- 2015