Blockade of metabotropic @entity3264 receptor 5 protects against DNA damage in a @entity3788 -induced XXXX model.

@entity20821 @entity3264 @entity46985 @entity3788 @entity26 @entity12369 @entity2509 @entity898 @entity10092 @entity2845 @entity191 @entity179 @entity460 @entity18650 @entity35 @entity14889 @entity2359 @entity2383
UNASSIGNED: @entity3264 excitotoxicity contributes to the development of @entity191 ( @entity191 ) and pharmacological blockade of metabotropic @entity3264 receptor 5 ( @entity10092 ) has beneficial anti- @entity2845 effects in animal models of @entity191 ; however, the mechanism by which these antagonists alleviate @entity191 symptoms is largely unknown. In our study, the effects of @entity10092 inhibition on DNA damage were investigated in a @entity3788 -induced model of @entity191 . We first found that the selective @entity10092 antagonist, @entity12369 , prevented @entity3788 -induced DNA damage in MN9D dopaminergic neurons through a mechanism involving the downregulation of intracellular @entity460 release which was associated with a reduction in endoplasmic reticulum stress and reactive @entity26 species (ROS)-related @entity2383 . Interestingly, the ROS-related @entity2383 was accompanied by an increase in expression of the antioxidant protein, Trx2. Treatment of cells with the @entity460 chelating agent @entity18650 or the ROS scavenger @entity898 , also reduced @entity3788 -induced DNA damage, while transfection of a dominant-negative form of Trx2 increased it. In addition, @entity10092 inhibition altered the expression profiles of proteins involved in DNA repair activity. Specifically, the expression of phosphorylated @entity2509 (p- @entity2509 ) and @entity14889 , as well as APE1 and @entity46985 were elevated after @entity3788 stimulation and were subsequently downregulated following blockade of @entity10092 . These findings were confirmed in vivo in a @entity3788 -induced @entity35 model of @entity191 . Inhibition of @entity10092 protected against @entity2359 by mitigating oxidative stress-related DNA damage associated with @entity20821 production and also reduced p- @entity2509 activity and Trx2 expression. These findings provide a novel link between @entity10092 and DNA damage in a model of @entity191 , and reveal a potential mechanism by which @entity10092 mediates DNA damage in @entity179 .
