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Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia- and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model

Authors
 Kwang Suk Lim ; Min-Ji Cha ; Yong-Hee Kim ; Ki-Chul Hwang ; Taiyoun Rhim ; Ji-Won Chae ; Eun Jeong Park ; Jang Kyoung Kim 
Citation
 Journal of Controlled Release, Vol.169(3) : 306~312, 2013 
Journal Title
 Journal of Controlled Release 
ISSN
 0168-3659 
Issue Date
2013
Abstract
Ischemic heart diseases caused by insufficient oxygen supply to the cardiac muscle require pharmaceutical agents for the prevention of the progress and recurrence. Metallothionein (MT) has a potential as a protein therapeutic for the treatment of this disease due to its anti-oxidative effects under stressful conditions. In spite of its therapeutic potential, efficient delivery systems need to be developed to overcome limitations such as low transduction efficiency, instability and short half-life in the body. To enhance intra-cellular transduction efficiency, Tat sequence as a protein transduction domain (PTD) was fused with MT in a recombinant method. Anti-apoptotic and anti-oxidative effects of Tat-MT fusion protein were evaluated under hyperglycemia and hypoxia stress conditions in cultured H9c2 cells. Recovery of cardiac functions by anti-apoptotic and anti-fibrotic effects of Tat-MT was confirmed in an ischemia/reperfusion (I/R) rat myocardial infarction model. Tat-MT fusion protein effectively protected H9c2 cells under stressful conditions by reducing intracellular ROS production and inhibiting caspase-3 activation. Tat-MT fusion protein inhibited apoptosis, reduced fibrosis area and enhanced cardiac functions in I/R. Tat-MT fusion protein could be a promising therapeutic for the treatment of ischemic heart diseases.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86910
DOI
10.1016/j.jconrel.2013.01.023
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0168365913000503
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