Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia- and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model
- Authors
- Lim, Kwang Suk; Cha, Min-Ji; Kim, Jang Kyoung; Park, Eun Jeong; Chae, Ji-Won; Rhim, Taiyoun; Hwang, Ki-Chul; Kim, Yong-Hee
- Issue Date
- Aug-2013
- Publisher
- ELSEVIER
- Keywords
- Metallothionein; Protein transduction domain; Anti-oxidant; Ischemia/reperfusion; Myocardial infarction
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.169, no.3, pp.306 - 312
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 169
- Number
- 3
- Start Page
- 306
- End Page
- 312
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/162272
- DOI
- 10.1016/j.jconrel.2013.01.023
- ISSN
- 0168-3659
- 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.
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