Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells

Ana Juknat, Neta Rimmerman, Rivka Levy, Zvi Vogel*, Ewa Kozela

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties. Unlike Δ9-tetrahydrocannabinol (THC), CBD is devoid of psychotropic effects and has very low affinity for both cannabinoid receptors, CB1 and CB2. We have previously reported that CBD and THC have different effects on anti-inflammatory pathways in lipopolysaccharide-stimulated BV-2 microglial cells, in a CB 1/CB2 independent manner. Moreover, CBD treatment of BV-2 cells, was found to induce a robust change in the expression of genes related to oxidative stress, glutathione deprivation and inflammation. Many of these genes were shown to be controlled by Nrf2 and ATF4 transcription factors. Using the Illumina MouseRef-8 BeadChip platform, DAVID Bioinformatics and Ingenuity Pathway Analysis, we identified functional sets of genes and networks affected by CBD. A subset of genes was found to be regulated by the metal responsive element (MRE)-binding transcription factor-1 (MTF-1) and is shown to be related to zinc homeostasis. We found that CBD upregulates the expression of the mRNAs for metallothionein 2 (Mt2), N-myc-downstream regulated gene 1 and matrix metalloproteinase 23 as well as of the zinc transporters ZnT1/Slc30a1 and Zip4/Slc39a4 but downregulates the expression of the mRNA for the zinc transporter Zip10/Slc39a10 as well as for the zinc finger protein 472. Among these genes, ZnT1, Mt2 and the zinc transporters ZIPs are known to function together to control the intracellular zinc concentration. These results show that CBD, but much less so THC, affects the expression of genes involved in zinc homeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its antioxidant and anti-inflammatory effects.

Original languageAmerican English
Pages (from-to)923-930
Number of pages8
JournalNeurochemistry International
Volume61
Issue number6
DOIs
StatePublished - Nov 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and by the Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases. A.J. is supported by the Israeli Ministry for Absorption in Science.

Keywords

  • Cannabidiol
  • Matrix metalloproteinase 23
  • Metallothionein
  • Zinc transporters
  • Δ-Tetrahydrocannabinol

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