Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress.
Recent studies demonstrate that cellular, molecular and morphological changes induced by stress in rats are accelerated when there is a pre-existing strain upon their already compromised adaptive responses to internal or external stimuli, such as may occur with uncontrolled diabetes mellitus. The deleterious actions of diabetes and stress may increase oxidative stress in the 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 polyclonal antisera that recognize proteins conjugated by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE). Radioimmunocytochemistry revealed that HNE protein conjugation is increased in all subregions of the hippocampus of streptozotocin (STZ) diabetic rats, rats subjected to restraint stress and STZ 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 utilization, 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 significant 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. Collectively, these results demonstrate that the hippocampus is vulnerable to increases in oxidative stress produced by diabetes and stress. In addition, increases in HNE protein conjugation of GLUT3 provide a potential mechanism for stress- and diabetes-mediated decreases in hippocampal neuronal glucose utilization.
Reagan
L P
LP
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, Box 165, 1230 York Avenue, New York, NY, USA. reaganl@rockvax.rockefeller.edu
Magariños
A M
AM
Yee
D K
DK
Swzeda
L I
LI
Van Bueren
A
A
McCall
A L
AL
McEwen
B S
BS
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D003432:Cross-Linking Reagents / Q000378:metabolism*; D018891:Dentate Gyrus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D051274:Glucose Transporter Type 3; D006706:Homeostasis / Q000502:physiology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009490:Neurosecretory Systems / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017966:Pyramidal Cells / Q000737:chemistry / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism*
D000447:Aldehydes; D003432:Cross-Linking Reagents; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495690:Slc2a3 protein, rat; C027576:4-hydroxy-2-nonenal