Autophagy after experimental intracerebral hemorrhage

被引:111
|
作者
He, Yangdong [1 ]
Wan, Shu [1 ]
Hua, Ya [1 ]
Keep, Richard F. [1 ]
Xi, Guohua [1 ]
机构
[1] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA
来源
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2008年 / 28卷 / 05期
关键词
autophagy; cathepsin D; deferoxamine; iron; intracerebral hemorrhage; microtubule-associated protein light chain 3;
D O I
10.1038/sj.jcbfm.9600578
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Autophagy contributes to ischemic brain injury, but it is not clear if autophagy occurs after intracerebral hemorrhage (ICH). This study examined whether ICH-induced cell death is partly autophagic. It then examined the role of iron in inducing this form of cell death after ICH. Male, adult Sprague-Dawley rats received an infusion of autologous whole blood or ferrous iron into the right basal ganglia. Control rats (sham) had a needle insertion. The rats were killed at 1, 3, 7, or 28 days later. Some rats were treated with either deferoxamine or vehicle after ICH. Microtubule-associated protein light chain-3 (LC3), a biomarker of autophagosome, and cathepsin D, a lysosomal biomarker, were measured by Western blot analysis and immunohistochemistry. Immunofluorescent double-labeling was used to identify the cell types expressing cathepsin D. Electron microscopy was performed to examine the cellular ultrastructure changes after ICH. We found that conversion of LC3-I to LC3-II, cathepsin D expression, and vacuole formation are increased in the ipsilateral basal ganglia after ICH. Intracerebral infusion of iron also resulted in enhanced conversion of LC3-I to LC3-II and increased cathepsin D levels. Deferoxamine (an iron chelator) treatment significantly reduced the conversion of LC3-I to LC3-II and cathepsin D levels after ICH. Our results demonstrated that autophagy occurs after ICH, and iron has a key role in ICH-induced autophagy. This also suggests that iron-induced autophagy may play a role in brain injury in other diseases associated with iron overload.
引用
收藏
页码:897 / 905
页数:9
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