Reduction of renal superoxide dismutase in progressive diabetic nephropathy.
Authors Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, Breyer MD,
Harris RC, Yamada Y, Takahashi T
Submitted By Takamune Takahashi on 3/24/2010
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2009
Date Published 6/1/2009
Volume : Pages 20(6) : 1303 - 1313
PubMed Reference 19470681
Abstract Superoxide excess plays a central role in tissue damage that results from
diabetes, but the mechanisms of superoxide overproduction in diabetic
nephropathy (DN) are incompletely understood. In the present study, we
investigated the enzyme superoxide dismutase (SOD), a major defender against
superoxide, in the kidneys during the development of murine DN. We assessed SOD
activity and the expression of SOD isoforms in the kidneys of two diabetic mouse
models (C57BL/6-Akita and KK/Ta-Akita) that exhibit comparable levels of
hyperglycemia but different susceptibility to DN. We observed down-regulation of
cytosolic CuZn-SOD (SOD1) and extracellular CuZn-SOD (SOD3), but not
mitochondrial Mn-SOD (SOD2), in the kidney of KK/Ta-Akita mice which exhibit
progressive DN. In contrast, we did not detect a change in renal SOD expression
in DN-resistant C57BL/6-Akita mice. Consistent with these findings, there was a
significant reduction in total SOD activity in the kidney of KK/Ta-Akita mice
compared with C57BL/6-Akita mice. Finally, treatment of KK/Ta-Akita mice with a
SOD mimetic, tempol, ameliorated the nephropathic changes in KK/Ta-Akita mice
without altering the level of hyperglycemia. Collectively, these results
indicate that down-regulation of renal SOD1 and SOD3 may play a key role in the
pathogenesis of DN.

Investigators with authorship
Matthew BreyerEli Lilly and Company
Raymond HarrisVanderbilt University
Takamune TakahashiVanderbilt University


Sod1superoxide dismutase 1, soluble
Sod2superoxide dismutase 2, mitochondrial
Sod3superoxide dismutase 3, extracellular