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The combination of metallothionein and superoxide dismutase protects pancreatic β cells from oxidative damage
Author(s) -
Park Leejin,
Min Dongsoo,
Kim Hyunok,
Park Jinseu,
Choi Sooyoung,
Park Yongsoo
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1254
Subject(s) - oxidative stress , superoxide dismutase , pancreatic islets , reactive oxygen species , chemistry , transplantation , islet , propidium iodide , apoptosis , viability assay , programmed cell death , microbiology and biotechnology , medicine , endocrinology , biochemistry , diabetes mellitus , biology
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. Copyright © 2011 John Wiley & Sons, Ltd.