Pax6 affects Ras-Raf-ERK1/2 in mouse aging brain.

Abstract

Pax6, a transcription factor and multifunctional protein, changes during aging. It also interacts with regulator proteins involved in cell metabolism and survival signalling pathways including Ras-GAP. Many forms of Ras, Raf and ERK1/2 are known but information on their region-specific expression patterns are unavailable from brain during aging. Therefore, it has been intended to evaluate expressions of Pax6 and forms of Ras, Raf, ERK1/2 in hippocampus, caudate nucleus, amygdale, cerebral cortex, cerebellum and olfactory lobe. Association of Pax6 with Ras, Raf and ERK1/2 was evaluated in co-culture (PC-12, C6-glia, U-87 MG) of neuroglia cell lines. Impacts of Pax6 were evaluated by siRNA mediated knockdown and expression patterns Ras-Raf-Erk1/2. Analysis of activities of Pax6 and impacts of 5'AMP, wild-type and mutant ERK were done by RT-PCR and luciferase reporter assay. Results indicate age-dependent changes of Pax6, Ras, Raf, ERK1/2 in different regions of brain of young and old mice. Erk1/2 shows synergistic activities to Pax6.