title: Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia- and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model.
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.
authors: Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors: Kwang Suk
authors: KS
authors: Lim
authors: Min-Ji
authors: MJ
authors: Cha
authors: Jang Kyoung
authors: JK
authors: Kim
authors: Eun Jeong
authors: EJ
authors: Park
authors: Ji-Won
authors: JW
authors: Chae
authors: Taiyoun
authors: T
authors: Rhim
authors: Ki-Chul
authors: KC
authors: Hwang
authors: Yong-Hee
authors: YH
authors: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D015696:Gene Products, tat / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D006943:Hyperglycemia / Q000517:prevention & control; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D008668:Metallothionein