Glutamate-stimulated ROS production in neuronal cultures: interactions with lead and the cholinergic system.
Oxidative stress may be an important factor in several pathological brain conditions. A contributing factor in many such conditions is excessive glutamate release, and subsequent glutamatergic neuronal stimulation, that causes increased production of reactive oxygen species (ROS), oxidative stress, excitotoxicity and neuronal damage. Glutamate release is also associated with illnesses such as Alzheimer's disease, stroke, and brain injury. Glutamate may interact with an environmental toxin, lead, and this interaction may result in neuronal damage. Glutamate-induced ROS production is greatly amplified by lead in cultured neuronal cells. Alterations in protein kinase C (PKC) activity seem to be important both for glutamate-induced ROS production, and for the amplification of glutamate-induced ROS production by lead. It is possible that the neurotoxic effects of lead are amplified through glutamate-induced neuronal excitation. Cholinergic stimulation can also trigger ROS production in neuronal cells. PKC seems to play a key-role also in cholinergic-induced ROS production superoxide anion being the primary reactive oxygen species. There seems to be a close relationship between the responses of cholinergic muscarinic and glutamatergic receptors because glutamate receptor antagonists inhibit cholinergic-induced activation of human neuroblastoma cells. Glutamatergic neuronal stimulation may be a common final pathway in several brain conditions in which oxidative stress and ensuing excitotoxicity plays a role.
Savolainen
K M
KM
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Loikkanen
J
J
Eerikäinen
S
S
Naarala
J
J
D000818:Animals; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D007854:Lead / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D007854:Lead; D018698:Glutamic Acid