SUMO2/3 conjugation is an endogenous neuroprotective mechanism

被引:122
作者
Datwyler, Anna Lena [1 ]
Laettig-Tuennemann, Gisela [1 ]
Yang, Wei [2 ]
Paschen, Wulf [1 ,2 ]
Lee, Sabrina Lin Lin [1 ]
Dirnagl, Ulrich [1 ,3 ]
Endres, Matthias [1 ,3 ]
Harms, Christoph [1 ,3 ]
机构
[1] Charite, Ctr Stroke Res Berlin, Dept Expt Neurol, D-10115 Berlin, Germany
[2] Duke Univ, Med Ctr, Dept Anesthesiol, Multidisciplinary Neuroprotect Labs, Durham, NC 27710 USA
[3] Charite, Klin & Poliklin Neurol, Dept Expt Neurol, D-10115 Berlin, Germany
基金
美国国家卫生研究院;
关键词
endogenous neuroprotection; lentiviral microRNA delivery; oxygen-glucose deprivation; SUMO conjugation; FOCAL CEREBRAL-ISCHEMIA; PROTEIN SUMOYLATION; MODIFIER CONJUGATION; HYPOTHERMIA; PATHWAY; GROWTH; CELLS;
D O I
10.1038/jcbfm.2011.112
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Small ubiquitin-like modifier (SUMO) 2/3 but not SUMO1 conjugation is activated after transient cerebral ischemia. To investigate its function, we blocked neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary cortical neurons. Viability was unaffected by SUMO2/3 silencing unless neurons were stressed by transient oxygen-glucose deprivation (OGD). Both 15 and 45 minutes of OGD were tolerated by control microRNA-expressing neurons but damaged >60% of neurons expressing SUMO2/3 microRNA. Damaging OGD (75 minutes) increased neuronal loss to 54% (control microRNA) and to 99% (SUMO2/3 microRNA). This suggests that activation of SUMO2/3 conjugation is an endogenous neuroprotective stress response. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 2152-2159; doi:10.1038/jcbfm.2011.112; published online 24 August 2011
引用
收藏
页码:2152 / 2159
页数:8
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