The cannabinoid dexanabinol is an inhibitor of the nuclear factor-kappa B (NF-κB)

Eric Jüttler*, Ioana Potrovita, Victoria Tarabin, Simone Prinz, Tuan Dong-Si, George Fink, Markus Schwaninger

*Korrespondierende/r Autor/-in für diese Arbeit
33 Zitate (Scopus)

Abstract

Exogenous and endogenous cannabinoids have been shown to have neuroprotective effects in vitro and in vivo. Although many of the pharmacological effects of cannabinoids have been identified, the mechanism of neuroprotection still represents a controversy. Here we demonstrate for the first time protective effects of the synthetic cannabinoid dexanabinol by inhibiting apoptosis in a neuron-like cell line using nuclear staining and FACS analysis and in primary neurons. We provide further evidence of inhibition of nuclear factor-κkappa B (NF-κB) by dexanabinol: Dexanabinol inhibits (1) phosphorylation and degradation of the inhibitor of NF-κB IκBα and translocation of NF-κB to the nucleus; dexanabinol reduces (2) the transcriptional activity of NF-κB and (3) mRNA accumulation of the NF-κB target genes tumor necrosis factor-alpha and interleukin-6 (TNF-α and IL-6). Dexanabinol does not bind to cannabinoid (CB) receptors 1 and 2. To investigate the mechanism of action, we employed the non-antioxidant CB1 receptor agonist WIN 55,212-2 and the antioxidant cannabinol, which binds to CB1 receptors only weakly. Both cannabinoids mimicked the effect of dexanabinol on NF-κB and apoptosis. This suggests that neither the antioxidant properties of cannabinoids nor binding to CB1 or CB2 receptors are responsible for the inhibition of NF-κB activity and apoptosis. Our results clearly demonstrate that dexanabinol inhibits NF-κB. NF-κB has been shown to be involved in brain damage and to promote neuronal cell death in vitro and in in vivo models of ischemic and neurodegenerative neurological diseases.

OriginalspracheEnglisch
ZeitschriftNeuropharmacology
Jahrgang47
Ausgabenummer4
Seiten (von - bis)580-592
Seitenumfang13
ISSN0028-3908
DOIs
PublikationsstatusVeröffentlicht - 01.09.2004

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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