Lp. Reagan et al., Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress, BRAIN RES, 862(1-2), 2000, pp. 292-300
Recent studies demonstrate that cellular, molecular and morphological chang
es induced by stress in rats are accelerated when there is a pre-existing s
train upon their already compromised adaptive responses to internal or exte
rnal stimuli, such as may occur with uncontrolled diabetes mellitus. The de
leterious actions of diabetes and stress may increase oxidative stress in t
he brain, leading to increases in neuronal vulnerability. In an attempt to
determine if stress, diabetes or stress+diabetes increases oxidative stress
in the hippocampus, radioimmunocytochemistry was performed using polyclona
l antisera that recognize proteins conjugated by the lipid peroxidation pro
duct 4-hydroxy-2-nonenal (HNE). Radioimmunocytochemistry revealed that HNE
protein conjugation is increased in all subregions of the hippocampus of st
reptozotocin (STZ) diabetic rats, rats subjected to restraint stress and ST
Z diabetic rats subjected to stress. Such increases were not significant in
the cortex. Because increases in oxidative stress may contribute to stress
- and diabetes-mediated decreases in hippocampal neuronal glucose utilizati
on, we examined the stress/diabetes mediated HNE protein conjugation of the
neuron specific glucose transporter, GLUT3. GLUT3 immunoprecipitated from
hippocampal membranes of diabetic rats subjected to stress exhibited signif
icant increases in HNE immunolabeling compared to control rats, suggesting
that HNE protein conjugation of GLUT3 contributes to decreases in neuronal
glucose utilization observed during diabetes and exposure to stress. Collec
tively, these results demonstrate that the hippocampus is vulnerable to inc
reases in oxidative stress produced by diabetes and stress. In addition, in
creases in HNE protein conjugation of GLUT3 provide a potential mechanism f
or stress- and diabetes-mediated decreases in hippocampal neuronal glucose
utilization. (C) 2000 Published by Elsevier Science B.V. All rights reserve
d.