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

Reagan, Lawrence P.; Magariños, Ana Marı́a; Yee, Daniel K.; Swzeda, L I; Bueren, A. Van; McCall, Anthony L.; McEwen, Bruce S.

doi:10.1016/s0006-8993(00)02212-5

Cited by 113 publications

(62 citation statements)

References 34 publications

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“…The fact that the effects observed here were seen on an enriched membrane preparation (synaptosomes) suggests that this may be the case in stress-induced decrease in glucose uptake. The second possible mechanism for the inhibitory stress effects on glucose uptake is the oxidative damage of GLUT-3 evidenced by conjugation of 4-hydroxynonenal (HNE) (Mark et al, 1997) or other lipid peroxidation products released in brain in the same stress model used in this paper (daily immobilization for 6 h during 7 days) (Reagan et al, 2000). This has also been seen in other settings such as cultured hippocampal neurons exposed to Abeta (increased HNE production and conjugation to GLUT-3) (Mark et al, 1997).…”

Section: Discussionmentioning

confidence: 51%

“…This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons (ie, by impairing their ability to remove damaging glutamate from the synapse), which may be the case of our model. Two possible mechanisms have been proposed to explain the stress-induced decrease in GLUT-3 expression: modification in binding to plasma membrane (Horner et al, 1987) or oxidative attack by mediators released during stress (Reagan et al, 2000). The first possible mechanism of GLUTs regulation is mediated by translocation from the plasma membrane to intracellular sites, as demonstrated previously after GC treatment (Horner et al, 1987).…”

Section: Discussionmentioning

confidence: 84%

“…One of the possible mechanisms is the prevention of cerebral GLUT-3 oxidation, which occurs in stress (Reagan et al, 2000) as it has been demonstrated to occur in stressed brain (García-Bueno et al, 2005a, b).…”

Section: Discussionmentioning

confidence: 99%

“…Succesful synaptosomal preparations were verified by determining expression of membrane associated protein synaptophysin (Sigma, 1:5000) and the absence of the cytoplasmatic protein B-tubulin (Sigma, 1:1000) (Reagan et al, 2000). Synaptophysin was used as loading control.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

García‐Bueno

Caso

Perez‐Nievas

et al. 2006

Neuropsychopharmacol

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Repeated stress causes an energy-compromised status in the brain, with a decrease in glucose utilization by the brain cells, which might account for excitotoxicity processes seen in this condition. In fact, brain glucose metabolism mechanisms are impaired in some neurodegenerative disorders, including stress-related neuropsychopathologies. More recently, it has been demonstrated that some synthetic peroxisome proliferator-activated receptor gamma (PPARg) agonists increase glucose utilization in rat cortical slices and astrocytes, as well as inhibit brain oxidative damage after repeated stress, which add support for considering these drugs as potential neuroprotective agents. To assess if stress causes glucose utilization impairment in the brain and to study the mechanisms by which this effect is achieved, young-adult male Wistar rats (control and immobilized for 6 h during 7 or 14 consecutive days, S7, S14) were i.p. injected with the natural ligand 15-deoxy-D-12,14-prostaglandin J 2 (PGJ 2 , 120 mg/kg) or the high-affinity ligand rosiglitazone (RG, 3 mg/kg) at the onset of stress. Repeated immobilization during 1 or 2 weeks produces a decrease in brain cortical synaptosomal glucose uptake, and this effect was prevented by treatment with both natural and synthetic PPARg ligands by restoring protein expression of the neuronal glucose transporter, GLUT-3 in membrane fractions. On the other hand, treatment with PPARg ligands prevents stress-induced ATP loss in rat brain. Finally, repeated immobilization stress also produces a decrease in brain cortical synaptosomal glutamate uptake, and this effect was prevented by treatment with PPARg ligands by restoring synaptosomal protein expression of the glial glutamate transporter, EAAT2. In summary, our results demonstrate that 15d-PGJ 2 and the thiazolidinedione rosiglitazone increase neuronal glucose metabolism, restore brain ATP levels and prevent the impairment in glutamate uptake mechanisms induced by exposure to stress, suggesting that this class of drugs may be therapeutically useful in conditions in which brain glucose levels or availability are limited after exposure to stress.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

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Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

García‐Bueno

Caso

Perez‐Nievas

et al. 2006

Neuropsychopharmacol

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“…In this vein, the implication of constitutive COX-2 expression in the brain and its upregulation by stress could also be physiological (reviewed in Dubois et al, 1998), a question that deserves further consideration. In fact, a kind of 'oxidative stress' occurs in the normal brain (Reagan et al, 2000), and evidence for a physiological or pathophysiological role for lipid peroxidation has been presented (reviewed in Parola et al, 1999) in addition to its well-defined deleterious consequences (reviewed in Mattson, 1998).…”

Section: Discussionmentioning

confidence: 99%

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Madrigal

Moro

Lizasoaín

et al. 2003

Neuropsychopharmacol

135

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Cyclooxygenase (COX) is the rate-limiting enzyme in the metabolism of arachidonic acid into prostanoids. Although it is constitutively expressed in brain neurons, the inducible isoform (COX-2) is also upregulated in pathological conditions such as seizures, ischemia or some degenerative diseases. To assess whether COX-2 is regulated after stress, we have used adult male Wistar rats, some of which were immobilized during 6 h. An increase in PGE 2 concentration occurs in brain cortex after 2-6 h of the onset of stress as well as an enhancement of COX-2 protein. Immunohistochemical studies indicate that COX-2 is expressed in the cortex and hippocampus after stress in cells with morphology of neurons. Administration of PDTC (150 mg/kg), an inhibitor of the transcription factor NF-kB or MK-801 (0.2 mg/kg), an N-methyl-D-aspartate receptor blocker, prevents both stress-induced increase in COX-2 activity and protein levels, suggesting an implication of these factors in the mechanism by which stress induces COX-2 in brain. To assess if COX-2 accounts for the oxidative status seen in brain after stress, a group of animals were i.p. injected with NS-398, a specific COX-2 inhibitor 1 h prior to the onset of stress. NS-398 (5 mg/kg) decreases stress-induced malondialdehyde accumulation in cortex as well as prevents the stressinduced oxidation of glutathione. Finally, NS-398 reduced Ca 2+ -independent inducible nitric oxide synthase (iNOS, NOS-2) activity and lowered the stress-induced accumulation of NO metabolite levels in cortex. These effects of NS-398 seem to be due to the specific inhibition of COX-2, since it has no effect on stress-induced corticosterone release, glutamate release, and NF-kB activation. These findings are discussed as possible damaging and/or adaptive roles for stress-induced COX-2 in the brain.

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Antioxidant Nutraceuticals as Novel Neuroprotective Agents

Katiyar

Ghosh

Saini

et al. 2022

Handbook of Nutraceuticals and Natural Products

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

Cited by 113 publications

References 34 publications

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

Induction of Cyclooxygenase-2 Accounts for Restraint Stress-Induced Oxidative Status in Rat Brain

Antioxidant Nutraceuticals as Novel Neuroprotective Agents

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