Molecular study of the interaction between insulin and Aβ neurotoxicity in primary hippocampal cell culture, considering Akt and ERK signaling pathways

摘要: INTRODUCTION ACCUMULATING EVIDENCES HAVE IMPLIED THAT INSULIN SIGNALING PLAYS A KEY ROLE IN THE PATHOLOGY OF AD. BUT THE DIRECT PROTECTIVE EFFECTS OF INSULIN AGAINST AB NEUROTOXICITY AND THE INVOLVE MECHANISMS STILL REMAINED TO BE ELUCIDATED. METHOD IN PRESENT CELL CULTURE STUDY AB INDUCED NEUROTOXICITY AND INSULIN MEDIATED NEUROPROTECTION WAS INVESTIGATED IN THE ISOLATED HIPPOCAMPAL CELL, CELL VIABILITY WAS ASSESSED BY MTT ASSAY AND ERK AND AKT AS WELL AS CASPASE-3 ACTIVITY WAS ASSESSED BY WESTERN BLOTTING. FINALLY, WITH INHIBITION OF PI3K/AKT AND ERK PATHWAY ROLES AND INTERACTION OF THESE PATHWAYS IN THE AB NEUROTOXICITY AND INSULIN MEDIATED NEUROPROTECTION WAS INVESTIGATED. RESULTS WESTERN BLOT ANALYSES REVEALED THAT AB25-35 INDUCED ELEVATION OF CASPASE-3 AND ELEVATE ERK ACTIVITY AND DECREASE AKT ACTIVITY. RESULTS ALSO SHOWED INSULIN PREVENT ERK AND CASPASE-3 ACTIVATION AND REVERSED AKT ACTIVITY. ON THE OTHER HAND STUDY WITH INHIBITORS SHOWED THAT WHILE PI3K/AKT PATHWAY PLAYS A PIVOTAL ROLE IN INSULIN MEDIATED NEUROPROTECTION, ERK ACTIVITY PARTICIPATES IN THE AB25-35 NEUROTOXICITY. CONCLUSION COLLECTIVELY THIS STUDY DISCLOSED THAT INSULIN TREATMENT IS AN EFFECTIVE FACTOR AGAINST AB-INDUCED NEUROTOXICITY AND THESE EFFECTS ARE ACHIEVED VIA INHIBITION OF PERSISTENT …