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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  ;  Jang Kyoung Kim  ;  Eun Jeong Park  ;  Ji-Won Chae  ;  Taiyoun Rhim  ;  Ki-Chul Hwang  ;  Yong-Hee Kim 
Citation
 JOURNAL OF CONTROLLED RELEASE, Vol.169(3) : 306-312, 2013 
Journal Title
 JOURNAL OF CONTROLLED RELEASE 
ISSN
 0168-3659 
Issue Date
2013
MeSH
Animals ; Apoptosis/drug effects ; Cell Line ; Gene Products, tat/genetics ; Gene Products, tat/pharmacology ; Gene Products, tat/therapeutic use ; Hyperglycemia/prevention & control ; Male ; Metallothionein/genetics ; Metallothionein/pharmacology ; Metallothionein/therapeutic use* ; Mice ; Myocardial Reperfusion Injury/drug therapy* ; Myocardial Reperfusion Injury/pathology* ; Myocardium/pathology* ; Oxidative Stress/drug effects ; Protein Structure, Tertiary ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/pharmacology ; Recombinant Fusion Proteins/therapeutic use
Keywords
Metallothionein ; Protein transduction domain ; Anti-oxidant ; Ischemia/reperfusion ; Myocardial infarction
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0168365913000503
DOI
10.1016/j.jconrel.2013.01.023
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Cha, Min Ji(차민지)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86910
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