title: Dual-mode enhancement of metallothionein protein with cell transduction and retention peptide fusion.
abstract: Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), have been developed as effective systems for delivering bio-active cargos such as proteins, genes and particles. Further improvements on cell-specific targeting, intracellular organelle targeting and intracellular retention are still necessary to enhance the therapeutic effect of PTD fusion proteins. In order to enhance the cell transduction and retention of anti-oxidative metallothionein protein (MT), MT was recombinantly fused with transcriptional activator (Tat) with or without a short peptide (sMTS) derived from mitochondria malate dehydrogenase (mMDH). Cellular uptake and retention time of fusion protein were significantly increased in the H9c2 cell by sMTS. The Tat-sMTS-MT (TMM) fusion protein protected H9c2 cells more effectively against hypoxia, hyperglycemia and combination compared with Tat-MT (TM) by reducing intracellular ROS level. It maintained the normal blood glucose level over an extended period of time in a streptozotocin-induced diabetic mouse model. PTD-sMTS-MT fusion protein has a potential to be used as a therapeutic protein for the treatment or prevention of diabetes and diabetic complications.
authors.affiliation: Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
authors.forename: Kwang Suk
authors.initials: KS
authors.lastname: Lim
authors.forename: Myoung-Hwa
authors.initials: MH
authors.lastname: Lim
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.forename: Jang Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Young Cheol
authors.initials: YC
authors.lastname: Kang
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Park
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Chae
authors.forename: So-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Seong-Eon
authors.initials: SE
authors.lastname: Ryu
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D015696:Gene Products, tat / Q000008:administration & dosage* / Q000235:genetics; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry; D008668:Metallothionein / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D057846:Cell-Penetrating Peptides; D015696:Gene Products, tat; D007004:Hypoglycemic Agents; D009842:Oligopeptides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D008668:Metallothionein; D008291:Malate Dehydrogenase
keywords: Antioxidant agent; Diabetic complications; Hypoxia; Metallothionein fusion protein; Protein transduction domain