title: The combination of metallothionein and superoxide dismutase protects pancreatic β cells from oxidative damage.
abstract: BACKGROUND
  Reactive oxygen species are considered an important cause of the death of pancreatic β cells, thereby triggering the development of type 2 diabetes as well as failure of islet transplantation. The biological properties of metallothionein (MT) and superoxide dismutase (SOD) are likely to be related to their antioxidant and free-radical scavenging abilities, but their access across biological membranes is limited.
  
  
  METHODS
  We investigated whether Tat-MT and Tat-SOD fusion protein could be introduced into islets by a novel protein transduction technology and protect them from oxidative damage. We used 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Annexin V/propidium iodide assays to analyse cell viability, and assessed expression of apoptosis marker proteins by Western blotting. We examined the protective effect of Tat-MT and Tat-SOD on the development of diabetes and on graft failure after syngeneic islet transplantation into Otsuka Long Evans Tokushima Fatty (OLETF) rats and Imprinting Control Region (ICR) mice, respectively.
  
  
  RESULTS
  Tat-MT and Tat-SOD were successfully delivered into the rat islets, and reactive oxygen species, nitric oxide, glucolipotoxicity-induced cell death, cytokine injury, and DNA fragmentation due to ischaemia-reperfusion in pancreatic β cells were significantly reduced. In addition Tat-MT and Tat-SOD treatment protected OLETF rats from developing diabetes, and enhanced the survival of antioxidant-treated islets transplanted into the renal capsules of diabetic mice.
  
  
  CONCLUSIONS
  Transduction of Tat-MT and Tat-SOD proteins offers a new strategy for protecting against the development of diabetes by relieving oxidative stress.
authors: Department of Internal Medicine and Bioengineering, Hanyang University College of Medicine and Engineering, Seoul, Korea.
authors: Leejin
authors: L
authors: Park
authors: Dongsoo
authors: D
authors: Min
authors: Hyunok
authors: H
authors: Kim
authors: Jinseu
authors: J
authors: Park
authors: Sooyoung
authors: S
authors: Choi
authors: Yongsoo
authors: Y
authors: Park
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000517:prevention & control*; D015696:Gene Products, tat / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D015696:Gene Products, tat; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D008668:Metallothionein; D013482:Superoxide Dismutase