Chen Lei, Kis Bela, Hashimoto Hirofumi, Busija David W, Takei Yoshio, Yamashita Hiroshi, Ueta Yoichi
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Kitakyushu 807-8555, Japan.
Brain Res. 2006 May 1;1086(1):42-9. doi: 10.1016/j.brainres.2006.02.128. Epub 2006 Apr 17.
Adrenomedullin 2 (AM2, intermedin) is a recently identified new member of the calcitonin gene-related peptide family. We examined whether AM2 can attenuate the increased blood-brain barrier permeability and cerebral endothelial cell (CEC) death induced by oxidative stress in vitro. Hydrogen peroxide (H(2)O(2), 0.5 mM) induced a continuous decrease of the transendothelial electrical resistance (TEER) and resulted in intercellular gap formations in rat CECs co-cultured with astrocytes. AM2 induced cAMP and nitric oxide production, increased TEER, enhanced peripheral localization of F-actin bands, and attenuated the increased permeability induced by H(2)O(2). AM2 treatment preserved mitochondrial membrane potential and improved CEC viability in H(2)O(2) treated cultures. These effects of AM2 were similar to those what were reported for adrenomedullin. These results suggest that AM2 protects CECs against oxidative injury in vitro.
肾上腺髓质素2（AM2，中间介质）是降钙素基因相关肽家族中最近发现的新成员。我们研究了AM2是否能减轻体外氧化应激诱导的血脑屏障通透性增加和脑内皮细胞（CEC）死亡。过氧化氢（H₂O₂，0.5 mM）导致跨内皮电阻（TEER）持续降低，并在与星形胶质细胞共培养的大鼠CEC中导致细胞间隙形成。AM2诱导cAMP和一氧化氮产生，增加TEER，增强F-肌动蛋白带的外周定位，并减轻H₂O₂诱导的通透性增加。AM2处理可维持线粒体膜电位并改善H₂O₂处理培养物中的CEC活力。AM2的这些作用与肾上腺髓质素报道的作用相似。这些结果表明，AM2在体外可保护CEC免受氧化损伤。
