NDLI: JWH-133, a Selective Cannabinoid CB$_{2}$ Receptor Agonist, Exerts Toxic Effects on Neuroblastoma SH-SY5Y Cells

Content Provider	Springer Nature Link
Author	Wojcieszak, Jakub Krzemień, Wojciech Zawilska, Jolanta B.
Copyright Year	2016
Abstract	Endocannabinoid system plays an important role in the regulation of diverse physiological functions. Although cannabinoid type 2 receptors (CB$_{2}$) are involved in the modulation of immune system in peripheral tissues, recent findings demonstrated that they are also expressed in the central nervous system and could constitute a new target for the treatment of neurodegenerative disorders. At present, very little is known about the potential effects of CB$_{2}$-mimetic drugs on neuronal cells. This study aimed to examine whether JWH-133, a selective CB$_{2}$ receptor agonist, affects the survival of SH-SY5Y neuroblastoma cell line, a widely used experimental in vitro model to study mechanisms of toxicity and protection in nigral dopaminergic neurons. Cell viability was assessed using two complementary methods: MTT test measuring mitochondrial activity and LDHe test indicating disruption of cell membrane integrity. In addition, cell proliferation was measured using BrdU incorporation assay. JWH-133 (10–40 μM) induced a concentration-dependent decrease of SH-SY5Y cell viability and proliferation rate. Using AM-630, a reverse agonist of CB$_{2}$ receptors, as well as Z-VAD-FMK, a pan-caspase inhibitor, we demonstrated that the cytotoxic effect of JWH-133 presumably was not mediated by activation of CB$_{2}$ receptors or by caspase pathway. Results of this work suggest that agonists of CB$_{2}$ receptors when administered in multiple/high doses may induce neuronal damage.
Starting Page	441
Ending Page	445
Page Count	5
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	58
Issue Number	4
e-ISSN	15591166
Language	English
Publisher	Springer US
Publisher Date	2016-02-03
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cytotoxicity JWH-133 Cannabinoid receptors SH-SY5Y cells Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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