Manev H, Uz T, Qu T
The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA.
Exp Gerontol. 2000 Dec;35(9-10):1201-9. doi: 10.1016/s0531-5565(00)00152-2.
Recent research has identified in central nervous system neurons the expression of two enzymes from the inflammatory pathway of the metabolism of arachidonic acid, the 5-lipoxygenase (5LOX) and the cyclooxygenase-2 (COX2). Expression of both enzymes appears to be upregulated during aging; upregulated 5LOX/COX2 expression in neurons may be responsible for the increased neuronal vulnerability to degeneration. Involvement of the excitatory neurotransmitter glutamate in aging-associated neurodegeneration has also been suggested. Stimulation of glutamate receptors by kainic acid (kainate) has been shown independently to affect the brain expression of 5LOX or COX2. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to measure the contents of mRNAs we found 3h after kainate injection (intraperitoneally; 10 mg/kg) increased mRNA levels of 5LOX and COX2, but not that of COX1 in the hippocampus of rats. Pretreatment with the COX2 inhibitor NS-398 (9 mg/kg, 1h prior to kainate) inhibited the kainate-stimulated increase of 5LOX and COX2 mRNA levels. Our results indicate that hippocampal expression of both 5LOX and COX2 increases rather promptly when glutamate receptors are stimulated by kainate. The mechanism of how NS-398 inhibits this action of kainate should be further investigated.
最近的研究已经在中枢神经系统神经元中发现了来自花生四烯酸代谢炎症途径的两种酶的表达，即5-脂氧合酶（5LOX）和环氧化酶-2（COX2）。这两种酶的表达在衰老过程中似乎都会上调；神经元中5LOX/COX2表达上调可能是神经元对变性易感性增加的原因。兴奋性神经递质谷氨酸参与衰老相关神经变性也已被提出。已独立证明，海藻酸（ kainate）刺激谷氨酸受体会影响5LOX或COX2在脑中的表达。使用定量逆转录-聚合酶链反应（RT-PCR）测定法来测量mRNA含量，我们发现在海藻酸注射（腹腔内注射；10mg/kg）后3小时，大鼠海马中5LOX和COX2的mRNA水平升高，但COX1的mRNA水平未升高。用COX2抑制剂NS-398（9mg/kg，在海藻酸注射前1小时）预处理可抑制海藻酸刺激的5LOX和COX2 mRNA水平的升高。我们的结果表明，当谷氨酸受体被海藻酸刺激时，海马中5LOX和COX2的表达会相当迅速地增加。NS-398如何抑制海藻酸的这种作用的机制应进一步研究。
