He Y, Hua Y, Song S, Liu W, Keep R F, Xi G
Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2008;105:29-32. doi: 10.1007/978-3-211-09469-3_6.
Autophagy occurs in the brain after intracerebral hemorrhage (ICH). Iron is an important factor causing neuronal death and brain atrophy after ICH. In this study, we examined whether iron can induce autophagy in the hippocampus and in cultured neurons. For in vivo studies, rats received an infusion of either saline or ferrous iron into the right hippocampus and were killed 1, 3, or 7 days later for Western blot analysis of microtubule-associated protein light chain-3 (LC3). For in vitro studies, primary cultured cortex neurons from rat embryos were exposed to ferrous iron. Cells were used for Western blot analysis of LC3 and monodansylcadaverine (MDC) staining 24h later. Intrahippocampal injection of ferrous iron resulted in an increased conversion of LC3-I to LC3-II. Exposure of primary cultured neurons to ferrous iron also induced an enhanced conversion of LC3-I to LC3-II. MDC labeling showed an accumulation of MDC in cultured neurons exposed to ferrous iron. These results indicate that autophagy is induced by iron in neurons and that iron-induced autophagy may contribute to brain injury after ICH.
脑出血（ICH）后大脑会发生自噬。铁是导致脑出血后神经元死亡和脑萎缩的一个重要因素。在本研究中，我们检测了铁是否能在海马体和培养的神经元中诱导自噬。在体内研究中，给大鼠右侧海马体注入生理盐水或亚铁离子，1、3或7天后处死大鼠，用于对微管相关蛋白轻链3（LC3）进行蛋白质印迹分析。在体外研究中，将大鼠胚胎原代培养的皮层神经元暴露于亚铁离子。24小时后，将细胞用于LC3的蛋白质印迹分析和单丹磺酰尸胺（MDC）染色。海马体内注射亚铁离子导致LC3-I向LC3-II的转化增加。原代培养的神经元暴露于亚铁离子也诱导了LC3-I向LC3-II的转化增强。MDC标记显示，在暴露于亚铁离子的培养神经元中MDC有积累。这些结果表明，铁可在神经元中诱导自噬，且铁诱导的自噬可能导致脑出血后的脑损伤。
