Brautigam Vielska M, Frasier Chuenchanok, Nikodemova Maria, Watters Jyoti J
Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
J Neuroimmunol. 2005 Sep;166(1-2):113-25. doi: 10.1016/j.jneuroim.2005.05.012.
ATP is abundant in the extracellular fluid following brain injury, and it exerts potent modulatory effects on microglia, whose hyperactivation is thought to exacerbate neuronal damage. We show here that ATP decreases LPS-stimulated iNOS and COX-2 expression and reduces NO release in BV-2 microglia by a mechanism involving p38 MAP kinase. Further, we demonstrate that the inhibitory effects of ATP on NO production occur within 30 min of exposure and correlate with activation of the transcription factor CREB. Together, these data suggest that ATP may exert neuroprotective effects in the brain via a mechanism involving augmented activation of the p38/CREB pathway.
脑损伤后细胞外液中ATP含量丰富，它对小胶质细胞具有强大的调节作用，小胶质细胞的过度激活被认为会加剧神经元损伤。我们在此表明，ATP通过一种涉及p38丝裂原活化蛋白激酶的机制，降低LPS刺激的BV-2小胶质细胞中诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的表达，并减少一氧化氮（NO）的释放。此外，我们证明ATP对NO产生的抑制作用在暴露后30分钟内出现，并与转录因子CREB的激活相关。这些数据共同表明，ATP可能通过一种涉及增强p38/CREB途径激活的机制在大脑中发挥神经保护作用。
