title: Genistein inhibits Aβ₂₅₋₃₅ -induced neurotoxicity in PC12 cells via PKC signaling pathway.
abstract: 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 β (Aβ)-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 Aβ(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 Aβ(25-35)-treated PC12 cells. Pretreatment of Myr, a general PKC inhibitor, significantly attenuated the neuroprotective effect of genistein against Aβ(25-35)-treated PC12 cells. The present study indicates that PKC signaling pathway is involved in the neuroprotective action of genistein against Aβ(25-35)-induced toxicity in PC12 cells.
authors.affiliation: Institute of Basic Medical Sciences, Guangzhou Higher Education Mega Center, Guangdong Pharmaceutical University, 280 Wai Huan Dong Road, Guangzhou 510006, China.
authors.forename: Sijing
authors.initials: S
authors.lastname: Luo
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.forename: Weiliang
authors.initials: W
authors.lastname: Liao
authors.forename: Meishun
authors.initials: M
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D019833:Genistein; D011493:Protein Kinase C; D002118:Calcium