title: The effect of genistein on the content and activity of α- and β-secretase and protein kinase C in Aβ-injured hippocampal neurons.
abstract: Genistein (Gen), a derivative of soy isoflavone aglycone, has been shown to exert significant protective effect on Aβ-induced neurotoxicity and neuroinjury. However, its underlying mechanism remains elusive. The objective was to investigate the inhibitory effect of Gen on Aβ-induced neurotoxicity and to elucidate the underlying mechanism. Primary rat hippocampal neurons were pre-treated with Gen for 2 hr followed by incubation with Aβ 25-35 for an additional 24 hr. The cell viability was assessed by MTT assay. The content and activity of α-, β-secretase and protein kinase C (PKC) were measured, and the antagonistic effect of PKC inhibitor Myr was also analysed to clarify the molecular mechanism of Gen inhibition of Aβ-induced toxicity to hippocampal neurons. The results showed that pre-treatment with Gen significantly increased the cell viability and presented the best effect at the final concentration of 0.375 µg/mL. Gen increases the activity of α-secretase but down-regulates the β-secretase activity. It also enhances the expression and activity of PKC. Myr, a PKC inhibitor, partially blocks the activation effect of Gen. Gen exerts protective effect on Aβ-induced neurotoxicity via activating the PKC signalling pathway, which further regulates the activities of α- and β-secretase and thereby inhibits the formation and toxicity of Aβ.
authors.affiliation: Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Liao
authors.forename: Guifang
authors.initials: G
authors.lastname: Jin
authors.forename: Meishun
authors.initials: M
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000517:prevention & control; D010446:Peptide Fragments / Q000633:toxicity*; D061251:Primary Cell Culture; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D019833:Genistein; D011493:Protein Kinase C; D053829:Amyloid Precursor Protein Secretases