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Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells.
Neurochem Int. 2012 Nov; 61(6):923-30.NI

Abstract

Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties. Unlike Δ(9)-tetrahydrocannabinol (THC), CBD is devoid of psychotropic effects and has very low affinity for both cannabinoid receptors, CB(1) and CB(2). 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)/CB(2) 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.

Authors+Show Affiliations

The Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22178458

Citation

Juknat, Ana, et al. "Cannabidiol Affects the Expression of Genes Involved in Zinc Homeostasis in BV-2 Microglial Cells." Neurochemistry International, vol. 61, no. 6, 2012, pp. 923-30.
Juknat A, Rimmerman N, Levy R, et al. Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells. Neurochem Int. 2012;61(6):923-30.
Juknat, A., Rimmerman, N., Levy, R., Vogel, Z., & Kozela, E. (2012). Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells. Neurochemistry International, 61(6), 923-30. https://doi.org/10.1016/j.neuint.2011.12.002
Juknat A, et al. Cannabidiol Affects the Expression of Genes Involved in Zinc Homeostasis in BV-2 Microglial Cells. Neurochem Int. 2012;61(6):923-30. PubMed PMID: 22178458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol affects the expression of genes involved in zinc homeostasis in BV-2 microglial cells. AU - Juknat,Ana, AU - Rimmerman,Neta, AU - Levy,Rivka, AU - Vogel,Zvi, AU - Kozela,Ewa, Y1 - 2011/12/09/ PY - 2011/09/21/received PY - 2011/11/15/revised PY - 2011/12/01/accepted PY - 2011/12/20/entrez PY - 2011/12/20/pubmed PY - 2014/4/16/medline SP - 923 EP - 30 JF - Neurochemistry international JO - Neurochem Int VL - 61 IS - 6 N2 - Cannabidiol (CBD) has been shown to exhibit anti-inflammatory, antioxidant and neuroprotective properties. Unlike Δ(9)-tetrahydrocannabinol (THC), CBD is devoid of psychotropic effects and has very low affinity for both cannabinoid receptors, CB(1) and CB(2). 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)/CB(2) 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. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/22178458/Cannabidiol_affects_the_expression_of_genes_involved_in_zinc_homeostasis_in_BV_2_microglial_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(11)00388-3 DB - PRIME DP - Unbound Medicine ER -