Effects of Bee Venom on Glutamate-Induced Toxicity in Neuronal and Glial Cells

Sang Min Lee,Seon Hwy Kim,Sun-Mi Choi,Jing Hua Jiang,Eun Jin Yang,Myung Gi Baek

doi:10.1155/2012/368196

Sang Min Lee, Seon Hwy Kim + Show 4 more

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https://doi.org/10.1155/2012/368196

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Abstract

Bee venom (BV), which is extracted from honeybees, is used in traditional Korean medical therapy. Several groups have demonstrated the anti-inflammatory effects of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS). Changes in glutamate release and uptake due to alterations in the activity of glutamate transporters have been reported in many neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell viability and signal transduction in glutamate-treated neuronal and microglial cells in the presence and absence of BV. We induced glutamatergic toxicity in neuronal cells and microglial cells and found that BV protected against cell death. Furthermore, BV significantly inhibited the cellular toxicity of glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK, ERK, and p38) following exposure to glutamate. These findings suggest that treatment with BV may be helpful in reducing glutamatergic cell toxicity in neurodegenerative diseases.

Highlights

Glutamate is well known as the main excitatory neurotransmitter in the central nervous system (CNS), where it plays an important role in brain functions including memory, synaptic plasticity, learning, and cognition
We reported that Bee venom (BV)-stimulated cell survival signaling pathways including the extracellular signal-regulated kinase (ERK) and AKT pathways and reduced neuronal cell death [19]
Recent reports on neurodegenerative diseases have shown that alterations in protein kinase expression and activity can modify the downstream activation of signaling proteins and trigger neuronal loss

Summary

Introduction

Glutamate is well known as the main excitatory neurotransmitter in the central nervous system (CNS), where it plays an important role in brain functions including memory, synaptic plasticity, learning, and cognition. Activated microglia from mice or macaques have been shown to express the excitatory amino acid transporter genes EAAT-1 and -2, suggesting that, similar to astrocytes, microglia take up glutamate and metabolize it to glutamine. Motor neuron death may be mediated by numerous toxic factors that originate from different cell types. Among these factors, a role for the dysregulation of glutamate homeostasis in amyotrophic lateral sclerosis- (ALS)mediated neurodegeneration has been established. We report that pretreatment of neuronal and microglial cells with BV significantly inhibited glutamate-mediated toxicity. Pretreatment with BV significantly inhibited the expression of JNK, ERK, and p38 in glutamate-stimulated N2a neuronal cells.

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