Ras and Raf, contain GREs which are activated upon binding of GRs. We evaluated the activity of GRs at Ras and Raf promoters using chromatin immunoprecipitation and real-time PCR and report decreased binding of the GR at these promoters. An ELISA-based GR binding assay was used to explore whether this decreased binding was restricted to in vivo promoters and revealed no differences Go6983 solubility dmso in binding of native GR to synthetic GREs. The decreased in vivo GR binding coincides with significantly decreased mRNA levels and slight reductions of protein of both H-Ras and Raf-1 in

perinatally arsenic-exposed mice. Nuclear activated extracellular-signal regulated kinase (ERK), a downstream target of Ras and Raf, whose transcriptional targets also play an important role in learning and memory, was decreased in the hippocampus of arsenic-exposed animals when compared to controls. GR-mediated transcriptional deficits in the MAPK/ERK pathway could be an underlying cause of previously reported learning deficits and provide the link to arsenic-induced deficiencies in cognitive development.

(C) 2011 Elsevier selleckchem Inc. All rights reserved.”
“Kynurenic acid (KYNA) is an endogenous metabolite of the kynurenine pathway for tryptophan degradation and an antagonist of both N-methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (alpha 7nACh) receptors. KYNA has also been shown to scavenge hydroxyl radicals (center dot OH) under controlled conditions of free radical production. In this work

we evaluated the ability of KYNA to scavenge superoxide anion (O(2)center dot(-)) and peroxynitrite (ONOO(-)). The scavenging ability of KYNA (expressed as IC(50) values) was as follows: center dot OH = O(2)center dot(-) > ONOO(-). In parallel, the antiperoxidative and scavenging capacities of KYNA (0-150 mu M) were tested in cerebellum and forebrain homogenates exposed to 5 mu M FeSO(4) and 2.5 mM 3-nitropropionic acid (3-NPA). Both FeSO(4) and 3-NPA increased lipid peroxidation (LP) and ROS formation Topoisomerase inhibitor in a significant manner in these preparations, whereas KYNA significantly reduced these markers. Reactive oxygen species (ROS) formation were determined in the presence of FeSO(4) and/or KYNA (0-100 mu M), both at intra and extracellular levels. An increase in ROS formation was induced by FeSO(4) in forebrain and cerebellum in a time-dependent manner, and KYNA reduced this effect in a concentration-dependent manner. To further know whether the effect of KYNA on oxidative stress is independent of NMDA and nicotinic receptors, we also tested KYNA (0-100 mu M) in a biological preparation free of these receptors – defolliculated Xenopus laevis oocytes – incubated with FeSO(4) for 1 h. A 3-fold increase in LP and a 2-fold increase in ROS formation were seen after exposure to FeSO(4), whereas KYNA attenuated these effects in a concentration-dependent manner.