Park Joon Ha, Shin Bich Na, Ahn Ji Hyeon, Cho Jeong-Hwi, Kim In Hye, Kim Dae Won, Won Moo-Ho, Hong Seongkweon, Cho Jun Hwi, Lee Choong-Hyun
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Department of Physiology, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea.
Cell Mol Neurobiol. 2016 Jul;36(5):821-8. doi: 10.1007/s10571-015-0265-8. Epub 2015 Nov 2.
Proline-rich Akt substrate of 40-kDa (PRAS40) is one of the important interactive linkers between Akt and mTOR signaling pathways. The increase of PRAS40 is related with the reduction of brain damage induced by cerebral ischemia. In the present study, we investigated time-dependent changes in PRAS40 and phospho-PRAS40 (p-PRAS40) immunoreactivities in the hippocampal CA1 region of the gerbil after 5 min of transient cerebral ischemia. PRAS40 immunoreactivity in the CA1 region was decreased in pyramidal neurons from 12 h after ischemic insult in a time-dependent manner, and, at 5 days post-ischemia, PRAS40 immunoreactivity was newly expressed in astrocytes. p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was hardly found 12 h and apparently detected again 1 and 2 days after ischemic insult. At 5 days post-ischemia, p-PRAS40 immunoreactivity in the CA1 pyramidal neurons was not found. These results indicate that ischemia-induced changes in PRAS40 and p-PRAS40 immunoreactivities in CA1 pyramidal neurons and astrocytes may be closely associated with delayed neuronal death in the hippocampal CA1 region following transient cerebral ischemia.
富含脯氨酸的40 kDa Akt底物(PRAS40)是Akt与mTOR信号通路之间重要的交互连接分子之一。PRAS40的增加与脑缺血诱导的脑损伤减轻相关。在本研究中,我们调查了沙土鼠短暂性脑缺血5分钟后海马CA1区PRAS40和磷酸化PRAS40(p-PRAS40)免疫反应性的时间依赖性变化。缺血性损伤后12小时起,CA1区锥体细胞中的PRAS40免疫反应性呈时间依赖性降低,并且在缺血后5天时,PRAS40免疫反应性在星形胶质细胞中重新表达。在缺血性损伤后12小时几乎未发现CA1锥体细胞中的p-PRAS40免疫反应性,而在缺血性损伤后1天和2天再次明显检测到。在缺血后5天时,未发现CA1锥体细胞中的p-PRAS40免疫反应性。这些结果表明,缺血诱导的CA1锥体细胞和星形胶质细胞中PRAS40和p-PRAS40免疫反应性变化可能与短暂性脑缺血后海马CA1区延迟性神经元死亡密切相关。