Adenosine and Oxygen/Glucose Deprivation in the Brain

Adenosine receptors A1 (A1AR) and A2a (A2aAR) play an important role in regulating glutamate uptake to avoid glutamate accumulation that causes excitotoxicity in the brain; however, the precise mechanism of the effects of A1AR and A2aAR is unclear. Herein, we report that expression of the A1AR protein in the astrocyte membrane and the level of intracellular glutamate were decreased, while expression of the A2aR protein was elevated in cells exposed to oxygen-glucose deprivation (OGD) conditions. Coimmunoprecipitation (Co-IP) experiments showed that A1AR interacts with A2aAR under OGD conditions. The activation of A1AR and inactivation of A2aAR by 2-chloro-N6-cyclopentyladenosine (CCPA) and SCH58251, respectively, partly reversed OGD-mediated glutamate uptake dysfunction, elevated EAAT2, and PPARγ protein levels, and suppressed the expression of Ying Yang 1 (YY1). Both the silencing of YY1 and the activation of PPARγ upregulated EAAT2 expression. Moreover, YY1 silencing elevated the PPARγ level under both normal and OGD conditions. Histone deacetylase (HDAC)1 was found to interact with YY1, and HDAC1 silencing improved PPARγ promoter activity. Taken together, our findings suggest that A1AR-A2aAR heteromers regulate EAAT2 expression and glutamate uptake through the YY1-mediated recruitment of HDAC1 to the PPARγ promoter region.

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Adenosine and Oxygen/Glucose Deprivation in the Brain

Adenosine Receptors in Neurodegenerative Diseases ◽

10.1016/b978-0-12-803724-9.00008-9 ◽

2017 ◽

pp. 151-173

Author(s):

Felicita Pedata ◽

Ilaria Dettori ◽

Irene Fusco ◽

Elisabetta Coppi ◽

Anna M. Pugliese ◽

...

Keyword(s):

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

The Brain

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Neuroprotective effects of magnesium on metabolic disturbances in fetal hippocampal slices after oxygen-glucose deprivation: Mediation by nitric oxide system

Journal of the Society for Gynecologic Investigation ◽

10.1016/s1071-5576(01)00161-7 ◽

2002 ◽

Vol 9 (2) ◽

pp. 86-92 ◽

Cited By ~ 12

Author(s):

Y Garnier

Keyword(s):

Nitric Oxide ◽

Hippocampal Slices ◽

Glucose Deprivation ◽

Oxide System ◽

Oxygen Glucose Deprivation ◽

Metabolic Disturbances ◽

Neuroprotective Effects ◽

Nitric Oxide System

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Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000119 ◽

2012 ◽

Vol 82 (4) ◽

pp. 267-274 ◽

Cited By ~ 5

Author(s):

Zahide Cavdar ◽

Mehtap Y. Egrilmez ◽

Zekiye S. Altun ◽

Nur Arslan ◽

Nilgun Yener ◽

...

Keyword(s):

Endothelial Cells ◽

Neuroprotective Effect ◽

Ischemia Reperfusion ◽

Neurovascular Unit ◽

Glucose Deprivation ◽

Matrix Metalloproteinase 2 ◽

Microvascular Endothelial Cells ◽

Oxygen Glucose Deprivation ◽

Microvascular Endothelial

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

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