Cuomo Ornella, Pignataro Giuseppe, Gala Rosaria, Boscia Francesca, Tortiglione Anna, Molinaro Pasquale, Di Renzo Gianfranco, Lytton Jonathan, Annunziato Lucio
Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
Ann N Y Acad Sci. 2007 Mar;1099:486-9. doi: 10.1196/annals.1387.051.
Sodium/calcium exchangers are neuronal plasma membrane transporters, which by coupling Ca2+ and Na+ fluxes, may play a relevant role in brain ischemia. The exchanger gene superfamily comprises two arms: the K+-independent (NCX) and K+-dependent (NCKX) exchangers. In the brain, three different NCX (NCX1, NCX2, NCX3) and three NCKX (NCKX2, NCKX3, NCKX4) family members have been described. Up to now, no sutides about the role played by NCKX proteins in cerebral ischemia have been published. The aim of the present study was to investigate the role of NCKX2 in an in vivo model of permanent middle cerebral artery occlusion (pMCAO). The role of this protein in the development of ischemic damage was assessed by knocking-down its expression with an antisense oligodeoxynucleotide (AS-ODN), intracerebroventricularly infused by an osmotic minipump for 48 h, starting from 24 h before pMCAO. The results showed that NCKX2 knocking-down by using antisense strategy increased the extent of the ischemic lesion. The results of this study suggest that NCKX2 could exert a neuroprotective effect during ischemic injury.
钠/钙交换体是神经元质膜转运蛋白，通过耦合Ca2+和Na+通量，可能在脑缺血中发挥重要作用。该交换体基因超家族包括两个分支：不依赖钾离子的（NCX）和依赖钾离子的（NCKX）交换体。在大脑中，已描述了三种不同的NCX（NCX1、NCX2、NCX3）和三种NCKX（NCKX2、NCKX3、NCKX4）家族成员。到目前为止，尚未发表关于NCKX蛋白在脑缺血中作用的研究。本研究的目的是在永久性大脑中动脉闭塞（pMCAO）的体内模型中研究NCKX2的作用。通过用反义寡脱氧核苷酸（AS-ODN）敲低其表达来评估该蛋白在缺血性损伤发展中的作用，从pMCAO前24小时开始，通过渗透微型泵脑室内注入48小时。结果表明，采用反义策略敲低NCKX2会增加缺血性病变的范围。本研究结果表明，NCKX2可能在缺血性损伤期间发挥神经保护作用。
