The combination of metallothionein and superoxide dismutase protects pancreatic beta cells from oxidative damage
- Title
- The combination of metallothionein and superoxide dismutase protects pancreatic beta cells from oxidative damage
- Author
- 박용수
- Keywords
- diabetes; rejection; Tat fusion protein; antioxidant; oxidative stress
- Issue Date
- 2011-11
- Publisher
- Wiley-Blackwell
- Citation
- Diabetes - Metabolism: Research and Reviews, Nov 01, 2011 27(8):P802-808
- Abstract
- Background Reactive oxygen species are considered an important cause of the death of pancreatic beta 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 beta 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. Copyright (C) 2011 John Wiley & Sons, Ltd.
- URI
- http://onlinelibrary.wiley.com/doi/10.1002/dmrr.1254/abstract?
- ISSN
- 1520-7560
- DOI
- 10.1002/dmrr.1254
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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