Savolainen K M, Loikkanen J, Eerikäinen S, Naarala J
Department of Pharmacology and Toxicology, University of Kuopio, Finland.
Neurotoxicology. 1998 Aug-Oct;19(4-5):669-74.
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.
氧化应激可能是几种脑部病理状况的重要因素。许多此类状况的一个促成因素是谷氨酸过度释放，以及随后的谷氨酸能神经元刺激，这会导致活性氧（ROS）生成增加、氧化应激、兴奋性毒性和神经元损伤。谷氨酸释放还与阿尔茨海默病、中风和脑损伤等疾病有关。谷氨酸可能与环境毒素铅相互作用，这种相互作用可能导致神经元损伤。在培养的神经元细胞中，铅会极大地放大谷氨酸诱导的ROS生成。蛋白激酶C（PKC）活性的改变似乎对谷氨酸诱导的ROS生成以及铅对谷氨酸诱导的ROS生成的放大都很重要。铅的神经毒性作用可能通过谷氨酸诱导的神经元兴奋而被放大。胆碱能刺激也可触发神经元细胞中的ROS生成。PKC似乎在胆碱能诱导的ROS生成中也起关键作用，超氧阴离子是主要的活性氧。胆碱能毒蕈碱受体和谷氨酸能受体的反应之间似乎存在密切关系，因为谷氨酸受体拮抗剂可抑制胆碱能诱导的人神经母细胞瘤细胞的激活。谷氨酸能神经元刺激可能是几种脑部状况的共同最终途径，在这些状况中氧化应激和随之而来的兴奋性毒性起作用。
