SOD2 Protects Neurons from Injury in Cell Culture and Animal Models of Diabetic
Authors Andrea M. Vincent, James W. Russell, Kelli A. Sullivan, Carey Backus, John M.
Hayes, Lisa L. McLean and Eva L. Feldman
Submitted By Eva Feldman on 9/19/2007
Status Published
Journal Experimental neurology
Year 2007
Date Published 12/1/2007
Volume : Pages 208 : 216 - 227
PubMed Reference 17927981
Abstract Hyperglycemia-induced oxidative stress is an inciting event in the development
of diabetic complications including diabetic neuropathy. Our observations of
significant oxidative stress and morphological abnormalities in mitochondria led
us to examine manganese superoxide dismutase (SOD2), the enzyme responsible for
mitochondrial detoxification of oxygen radicals. We demonstrate that over
expression of SOD2 decreases superoxide (O2.-) in cultured primary dorsal root
ganglion (DRG) neurons and subsequently blocks caspase-3 activation and cellular
injury. Under expression of SOD2 in dissociated DRG cultures from adult SOD2+/-
mice results in increased levels of O2.-, activation of caspase-3 cleavage and
decreased neurite outgrowth under basal conditions that are exacerbated by
hyperglycemia. These profound changes in sensory neurons led us to explore the
effects of decreased SOD2 on the development of diabetic neuropathy (DN) in
mice. DN was assessed in SOD2+/- C57BL/6J mice and their SOD2+/+ litter mates
following streptozotocin (STZ) treatment. These animals, while hyperglycemic, do
not display any signs of DN. DN was observed in the C57BL/6Jdb/db mouse, and
decreased expression of SOD2 in these animals increased DN. Our data suggest
that SOD2 activity is an important cellular modifier of neuronal oxidative
defense against hyperglycemic injury.

Investigators with authorship
Eva FeldmanUniversity of Michigan


Casp3caspase 3, apoptosis related cysteine protease
Sod2superoxide dismutase 2, mitochondrial