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Cannabidiol-induced apoptosis in murine microglial cells through lipid raft.
Glia. 2012 Jul; 60(7):1182-90.GLIA

Abstract

Cannabidiol (CBD), the major nonpsychotropic phytocannabinoid, induces apoptosis in both immortalized and primary lymphocytes and monocytes. However, contrasting effects of CBD on the apoptosis between normal and immortalized glial cells have been reported. This study investigated the proapoptotic effect of CBD on primary microglial cells. Treatment of murine primary microglial cultures with CBD resulted in a time- and concentration-dependent induction of apoptosis, as shown by increase in hypodiploid cells and DNA strand breaks, and marked activation of both caspase-8 and -9. Mechanistic studies revealed that antioxidants, including N-acetyl-L-cysteine and glutathione, the G protein-coupled receptor 55 agonist abnormal-CBD and specific antagonists for vanilloid, and CB1 and CB2 cannabinoid receptors did not counteract the apoptosis induced by CBD. In contrast, methyl-β-cyclodextrin (MCD), a lipid raft disruptor, potently attenuated CBD-induced microglial apoptosis and caspase activation. Furthermore, CBD induced lipid raft coalescence and augmented the expression of GM1 ganglioside and caveolin-1, all of which were attenuated by MCD. Taken together, these results suggest that CBD induces a marked proapoptotic effect in primary microglia through lipid raft coalescence and elevated expression of GM1 ganglioside and caveolin-1.

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Authors+Show Affiliations

Wu HY
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
Goble K
No affiliation info available
Mecha M
No affiliation info available
Wang CC
No affiliation info available
Huang CH
No affiliation info available
Guaza C
No affiliation info available
Jan TR
No affiliation info available

MeSH

AnimalsApoptosisCannabidiolCaspasesCaveolin 1Dose-Response Relationship, DrugMembrane MicrodomainsMiceMicrogliaReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2

Pub Type(s)

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

Language

eng

PubMed ID

22535572

Citation

Wu, Hsin-Ying, et al. "Cannabidiol-induced Apoptosis in Murine Microglial Cells Through Lipid Raft." Glia, vol. 60, no. 7, 2012, pp. 1182-90.
Wu HY, Goble K, Mecha M, et al. Cannabidiol-induced apoptosis in murine microglial cells through lipid raft. Glia. 2012;60(7):1182-90.
Wu, H. Y., Goble, K., Mecha, M., Wang, C. C., Huang, C. H., Guaza, C., & Jan, T. R. (2012). Cannabidiol-induced apoptosis in murine microglial cells through lipid raft. Glia, 60(7), 1182-90. https://doi.org/10.1002/glia.22345
Wu HY, et al. Cannabidiol-induced Apoptosis in Murine Microglial Cells Through Lipid Raft. Glia. 2012;60(7):1182-90. PubMed PMID: 22535572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol-induced apoptosis in murine microglial cells through lipid raft. AU - Wu,Hsin-Ying, AU - Goble,Kathleen, AU - Mecha,Miriam, AU - Wang,Chia-Chi, AU - Huang,Chung-Hsiung, AU - Guaza,Carmen, AU - Jan,Tong-Rong, Y1 - 2012/04/25/ PY - 2011/08/22/received PY - 2012/03/30/accepted PY - 2012/4/27/entrez PY - 2012/4/27/pubmed PY - 2012/9/21/medline SP - 1182 EP - 90 JF - Glia JO - Glia VL - 60 IS - 7 N2 - Cannabidiol (CBD), the major nonpsychotropic phytocannabinoid, induces apoptosis in both immortalized and primary lymphocytes and monocytes. However, contrasting effects of CBD on the apoptosis between normal and immortalized glial cells have been reported. This study investigated the proapoptotic effect of CBD on primary microglial cells. Treatment of murine primary microglial cultures with CBD resulted in a time- and concentration-dependent induction of apoptosis, as shown by increase in hypodiploid cells and DNA strand breaks, and marked activation of both caspase-8 and -9. Mechanistic studies revealed that antioxidants, including N-acetyl-L-cysteine and glutathione, the G protein-coupled receptor 55 agonist abnormal-CBD and specific antagonists for vanilloid, and CB1 and CB2 cannabinoid receptors did not counteract the apoptosis induced by CBD. In contrast, methyl-β-cyclodextrin (MCD), a lipid raft disruptor, potently attenuated CBD-induced microglial apoptosis and caspase activation. Furthermore, CBD induced lipid raft coalescence and augmented the expression of GM1 ganglioside and caveolin-1, all of which were attenuated by MCD. Taken together, these results suggest that CBD induces a marked proapoptotic effect in primary microglia through lipid raft coalescence and elevated expression of GM1 ganglioside and caveolin-1. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/22535572/Cannabidiol_induced_apoptosis_in_murine_microglial_cells_through_lipid_raft_ L2 - https://doi.org/10.1002/glia.22345 DB - PRIME DP - Unbound Medicine ER -