Journal
JOURNAL OF NEUROCHEMISTRY
Volume 126, Issue 4, Pages 437-450Publisher
WILEY
DOI: 10.1111/jnc.12324
Keywords
guanosine; oxygen; glucose deprivation and reoxygenation; glutamate uptake; adenosine receptors; mitogen-activated protein kinases signaling; hippocampal slices
Categories
Funding
- Brazilian funding agency CNPq (Conselho Nacional de Desenvolvimento Cientfico e Tecnologico) [01.06.0842-00]
- Brazilian funding agency INCT (Instituto Nacional de Ciencia e Tecnologia)
- Spanish Ministry of Science and Innovation [SAF2009-12150]
- Ministry of Education [PBH2007-0004-PC]
- Spanish Ministry of Health (Instituto de Salud Carlos III) [RETICS-RD06/0026]
- CAPES/DGU [173/2008]
Ask authors/readers for more resources
Guanosine (GUO) is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in in vivo and in vitro models of neurotoxicity. This study was designed to understand the neuroprotective mechanism of GUO against oxidative damage promoted by oxygen/glucose deprivation and reoxygenation (OGD). GUO (100 mu M) reduced reactive oxygen species production and prevented mitochondrial membrane depolarization induced by OGD. GUO also exhibited anti-inflammatory actions as inhibition of nuclear factor kappa B activation and reduction of inducible nitric oxide synthase induction induced by OGD. These GUO neuroprotective effects were mediated by adenosine A(1) receptor, phosphatidylinositol-3 kinase and MAPK/ERK. Furthermore, GUO recovered the impairment of glutamate uptake caused by OGD, an effect that occurred via a Pertussis toxin-sensitive G-protein-coupled signaling, blockade of adenosine A(2A) receptors (A(2A)R), but not via A(1) receptor. The modulation of glutamate uptake by GUO also involved MAPK/ERK activation. In conclusion, GUO, by modulating adenosine receptor function and activating MAPK/ERK, affords neuroprotection of hippocampal slices subjected to OGD by a mechanism that implicates the following: (i) prevention of mitochondrial membrane depolarization, (ii) reduction of oxidative stress, (iii) regulation of inflammation by inhibition of nuclear factor kappa B and inducible nitric oxide synthase, and (iv) promoting glutamate uptake.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available