Abstract
Glutamate is an excitatory neurotransmitter involved in neural function. Excess accumulation of intercellular glutamate leads to increasing concentration of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in neuronal cells. In this study, we investigated the antioxidant activity of several typical superior compounds among four neuronal cells, and determined the scavenging activity of free radicals. The in vivo assay was also carried out to compare the protective effect of glutamate-induced cell damage. Hierarchical clustering analysis was used to identify the common properties. Glutamate induced neurotoxicity and ROS production, suggesting glutamate cytotoxicity was related to oxidative stress and widely exists in different cell lines. Those screening compounds exhibited strong antioxidant ability, but low cytotoxicity to neuronal cells, acting as agents against neurodegenerative diseases. Finally, a hierarchical clustering analysis assay indicated that hyperoside and rutin hydrate are the most effective compounds for attenuating intercellular ROS levels. The results suggested the activity more or less relies on structure, rather than residues. These data generate new supporting ideas to remove intracellular ROS and the identified compounds serve as potential therapeutic agents in multiple neurological diseases.
Highlights
Glutamate, an inhibitory and excitatory neurotransmitter in the central nervous system (CNS), plays an essential role on regulating brain function, and contributes excitotoxicity in neuronal cells.[1,2,3] Excessive stimulation of intercellular glutamate is a leading factor, which is involved in neurodegenerative diseases of the CNS, including strokes, Alzheimer's disease and Parkinson's disease.[4,5] Glutamate acts as a neurotoxicant mainly by increasing the intracellular levels of reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) in neuronal cells.[6]
The cell viability experiment was performed to four typical neural cells, including PC22, SH-SY5Y, HT22 and primary astrocytes
Additional 100 mM glutamate to SH-SY5Y cells induced a sharp decrease of the cell viability, suggesting that SH-SY5Y was more resistant to glutamate than other cells
Summary
An inhibitory and excitatory neurotransmitter in the central nervous system (CNS), plays an essential role on regulating brain function, and contributes excitotoxicity in neuronal cells.[1,2,3] Excessive stimulation of intercellular glutamate is a leading factor, which is involved in neurodegenerative diseases of the CNS, including strokes, Alzheimer's disease and Parkinson's disease.[4,5] Glutamate acts as a neurotoxicant mainly by increasing the intracellular levels of reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) in neuronal cells.[6]. Oxidative stress can trigger the protease cascade events, results in protein misfolding, mitochondrial dysfunction. In those process, glutamate-induced neurodegenerative diseases and neuronal cell death is usually associated with oxidative stress.[8,9,10] The over accumulated ROS, as well as the oxidative stress, are tightly associated with inhibition of glutathione
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