Upregulation of myeloid cell leukemia-1 potentially modulates beclin-1-dependent autophagy in ischemic stroke in rats

BMC Neuroscience

Pei Zhong³  Huang Ruxun³  Zhang Xu¹  Huang Yi³  Ou Jingsong²  Su Huanxing⁴  Sun Xicui³  Chen Xingyong¹ 

[1] Department of Neurology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, PR China;Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China;Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, PR China;State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China

关键词: Cerebral ischemia;    Beclin-1;    Myeloid cell leukemia 1;   

Others  :  1140260
DOI  :  10.1186/1471-2202-14-56

 received in 2012-09-04, accepted in 2013-05-16,  发布年份 2013

【 摘 要 】

Background

The mechanisms that underlie autophagy in cerebral ischemia remain poorly defined. Myeloid cell leukemia-1 (Mcl1), an anti-apoptotic member of the Bcl-2 family of proteins, regulates the balance between autophagy and apoptosis. However, little is known regarding its expression profile and contribution to cell fate in the brain following ischemic stroke.

Results

In this study, we investigated the expression profile and cellular distribution of Mcl1 in brains from transient middle cerebral artery occlusion (MCAO) model rats. Brain slices from sham-operated control rats showed minimal immunoreactivity for Mcl1. Mcl1 was mainly produced in neurons. Immunoreactivity for Mcl1 increased as early as 4 hours after MCAO, peaked at 24 hours, and then declined, but still remained high, at 72 hours. Mcl1 positive cells never colocalized with either cleaved caspase-3 or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells. Both microtubule-associated protein 1 light chain 3 (LC3) and beclin-1 were evident in ischemic brain between 4 and 72 hours after MCAO. Most cells with strong LC3 staining were also labeled with beclin-1. Beclin-1 did colocalize with caspase-3 or Mcl1. Beclin-1/caspase-3 positive cells displayed the characteristic features of apoptosis including cell shrinkage and pyknotic nuclei, whereas beclin-1/Mcl1 positive cells had normal morphology. Pretreatment with 3-methyladenine attenuated autophagy without affecting the level of Mcl1 protein.

Conclusions

These findings demonstrate that the expression of Mcl1 is involved in the survival of neuronal cells. In addition, the coexpression of Mcl1 with beclin-1 may attenuate beclin-1-dependent autophagy during ischemic stroke in rats.

【 授权许可】

   
2013 Xingyong et al.; licensee BioMed Central Ltd.

【 图 表 】

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