Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress

Citation
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
Citations number
37
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
00068993 → ACNP
Volume
862
Issue
1-2
Year of publication
2000
Pages
292 - 300
Database
ISI
SICI code
0006-8993(20000417)862:1-2<292:OSAHCO>2.0.ZU;2-9
Abstract
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.