Genistein Inhibits Aβ25-35 -Induced Neurotoxicity in PC12 Cells via PKC Signaling Pathway

Protein kinase C (PKC) signaling pathway is recognized as an important molecular mechanism of Alzheimer's disease (AD) in the regulation of neuronal plasticity and survival. Genistein, the most active molecule of soy isoflavones, exerts neuroprotective roles in AD. However, the detailed mechanism has not been fully understood yet. The present study aimed to investigate whether the neuroprotective effects of genistein against amyloid beta (A beta)-induced toxicity in cultured rat pheochromocytoma (PC12) cells is involved in PKC signaling pathway. PC12 cells were pretreated with genistein for 2 h following incubation with A beta(25-35) for additional 24 h. Cell viability was assessed by MTT. Hoechst33342/PI staining was applied to determine the apoptotic cells. PKC activity, intracellular calcium level and caspase-3 activity were analyzed by assay kits. The results showed that pretreatment with genistein significantly increased cell viability and PKC activity, decreased the levels of intracellular calcium, attenuated Hoechst/PI staining and blocked caspase-3 activity in A beta(25-35)-treated PC12 cells. Pretreatment of Myr, a general PKC inhibitor, significantly attenuated the neuroprotective effect of genistein against A beta(25-35)-treated PC12 cells. The present study indicates that PKC signaling pathway is involved in the neuroprotective action of genistein against A beta(25-35)-induced toxicity in PC12 cells.