Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by dual activation of the ras-phosphoinositide 3-kinase and jun n-terminal kinase pathways.

摘要: Abstract Glutaredoxin 2 (Grx2) from Escherichia coli protects cerebellar neurons dopamine-induced apoptosis via nuclear factor kappa B (NF-κB) activation, which is mediated by the expression of redox factor-1 (Ref-1). An analysis mechanisms underlying Grx2 protective activity revealed dual activation signal transduction pathways. significantly activated Ras/phosphoinositide 3-kinase/Akt/NF-κB cascade in parallel to Jun N-terminal kinase (JNK)/AP1 cascade. Dopamine, comparison, down-regulated both Treatment with Ref-1 antisense oligonucleotide reduced ability activate Akt and AP-1 but had no effect on phosphorylation JNK1/2, suggesting that Akt/NF-κB are regulated Ref-1. Exposure JNK1/2 presence NF-κB DNA binding activities abolished protection. These results demonstrate 3-kinase cascades, Ref-1, an essential component mechanism action.