We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The combination of metallothionein and superoxide dismutase protects pancreatic [beta] cells from oxidative damage.
- Authors
Park, Leejin; Min, Dongsoo; Kim, Hyunok; Park, Jinseu; Choi, Sooyoung; Park, Yongsoo
- 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.
- Publication
Diabetes/Metabolism Research & Reviews, 2011, Vol 27, Issue 8, p802
- ISSN
1520-7552
- Publication type
Journal Article
- DOI
10.1002/dmrr.1254