Δ<sup>9</sup>‐Tetrahydrocannabinol induces apoptosis in C6 glioma cells

Sánchez, Cristina; Galve‐Roperh, Ismael; Canova, Cécile; Brachet, Philippe; Guzmán, Manuel

doi:10.1016/s0014-5793(98)01085-0

Cited by 269 publications

(189 citation statements)

References 32 publications

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“…It has long been known that cannabinoids, including THC, can stimulate the MAPK cascade in Chinese hamster ovary cells (13), rat and mouse hippocampus (14), rat primary astrocytes (43), human astrocytoma cells (44), transformed neural cells (16,45) human breast cancer cells (19), and the striatum (46). Furthermore, a recent report has shown evidence indicating that THC-induced apoptosis in certain types of leukemic cells is mediated by down-regulation of ERK (5).…”

Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

Jia

Hegde

Singh

et al. 2006

Molecular Cancer Research

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Plant-derived cannabinoids, including #9-tetrahydrocannabinol (THC), induce apoptosis in leukemic cells, although the precise mechanism remains unclear. In the current study, we investigated the effect of THC on the upstream and downstream events that modulate the extracellular signal-regulated kinase (ERK) module of mitogen-activated protein kinase pathways primarily in human Jurkat leukemia T cells. The data showed that THC down-regulated Raf-1/mitogenactivated protein kinase/ERK kinase (MEK)/ERK/RSK pathway leading to translocation of Bad to mitochondria.

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Section: Discussionmentioning

confidence: 99%

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

Jia

Hegde

Singh

et al. 2006

Molecular Cancer Research

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“…Activation of CB1 is known to release glutamate, though the mechanism of CB1-induced glutamate release has been controversial [34][35][36][37] . We wondered therefore whether CB1-induced glutamate release is due to TWIK-1/TREK-1 heterodimers.…”

Section: Twik-1 Is a Functional Channel In Astrocytesmentioning

confidence: 99%

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

et al. 2014

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TWIK-1 is a member of the two-pore domain K þ (K2P) channel family that plays an essential part in the regulation of resting membrane potential and cellular excitability. The physiological role of TWIK-1 has remained enigmatic because functional expression of TWIK-1 channels is elusive. Here we report that native TWIK-1 forms a functional channel at the plasma membrane of astrocytes. A search for TWIK-1-binding proteins led to the identification of TREK-1, another member of the K2P family. The TWIK-1/TREK-1 heterodimeric channel is formed via a disulphide bridge between residue C69 in TWIK-1 and C93 in TREK-1. Gene silencing demonstrates that surface expression of TWIK-1 and TREK-1 are interdependent. TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoidinduced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels.

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“…CB 1 receptor is primarily expressed in glutamatergic neurons and axon terminals of GABA interneurons in CNS (14). CB 1 receptor is also found in DA neurons (15) and nonneuronal cells, including microglia (16), astrocytes (17,18), and oligodendrocytes (19). This receptor is activated in response to endogenous ligands, which are mainly derivatives of polyunsaturated fatty acids, including anandamide (arachidonylethanolamide [AEA]) (20,21) and 2-arachidonoylglycerol (21,22).…”

Section: P Arkinson's Disease (Pd) Is a Common Neurodegenerativementioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

111

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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Δ⁹‐Tetrahydrocannabinol induces apoptosis in C6 glioma cells

Cited by 269 publications

References 32 publications

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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Δ9‐Tetrahydrocannabinol induces apoptosis in C6 glioma cells

Cited by 269 publications

References 32 publications

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

Δ9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

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Δ⁹‐Tetrahydrocannabinol induces apoptosis in C6 glioma cells