外体
蛋白酶体
微泡
间充质干细胞
蛋白质组
旁分泌信号
细胞生物学
分泌物
医学
生物
生物信息学
生物化学
内科学
基因
小RNA
受体
作者
Ruenn Chai Lai,S. G. Tan,Bao Ju Teh,Siu Kwan Sze,Fatih Arslan,Dominique P. V. de Kleijn,Andre Boon Hwa Choo,Sai Kiang Lim
出处
期刊:International Journal of Proteomics
[Hindawi Limited]
日期:2012-07-18
卷期号:2012: 1-14
被引量:384
摘要
Mesenchymal stem cells (MSCs) are used in many of the current stem cell-based clinical trials and their therapeutic efficacy has increasingly been attributed to secretion of paracrine factors. We have previously demonstrated that a therapeutic constituent of this secretion is exosome, a secreted bilipid membrane vesicle of ~ 50–100 nm with a complex cargo that is readily internalized by H9C2 cardiomyocytes. It reduces infarct size in a mouse model of myocardial ischemia/reperfusion (MI/R) injury. We postulate that this therapeutic efficacy is derived from the synergy of a select permutation of individual exosome components. To identify protein candidates in this permutation, the proteome was profiled and here we identified 20S proteasome as a protein candidate. Mass spectrometry analysis detected all seven α and seven β chains of the 20S proteasome, and also the three beta subunits of “immunoproteasome” with a very high confidence level. We demonstrated that a functional proteasome copurified with MSC exosomes with a density of 1.10–1.18 g/mL, and its presence correlated with a modest but significant reduction in oligomerized protein in a mouse model of myocardial infarction. Circulating proteasomes in human blood also copurified with exosomes. Therefore, 20S proteasome is a candidate exosome protein that could synergize with other constituents to ameliorate tissue damage.
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