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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

Title
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
Issue Date
2013
Journal Title
Journal of Controlled Release
ISSN
0168-3659
Citation
Journal of Controlled Release, Vol.169(3) : 306~312, 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://www.sciencedirect.com/science/article/pii/S0168365913000503

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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