PMID- 33605427 OWN - NLM STAT- MEDLINE DCOM- 20210830 LR - 20210830 IS - 1897-5631 (Electronic) IS - 0239-8508 (Linking) VI - 59 IP - 1 DP - 2021 TI - Genistein exerts a cell-protective effect via Nrf2/HO-1/ /PI3K signaling in Ab25-35-induced Alzheimer's disease models in vitro. PG - 49-56 LID - 10.5603/FHC.a2021.0006 [doi] AB - INTRODUCTION: Alzheimer's disease (AD), a very common neurodegenerative disorder, is mainly characterized by the deposition of b-amyloid protein (Ab) and extensive neuronal cell death. Currently, there are no satisfactory therapeutic approaches for AD. Although neuroprotective effects of genistein against Ab-induced toxicity have been reported, the underlying molecular mechanisms remain unclear. Furthermore, the PI3K/Akt/Nrf2 signaling pathway is associated with AD. The aim of the study was to investigate whether genistein can modulate Nrf2/HO-1/PI3K signaling to treat AD. MATERIALS AND METHODS: Cell viability assay, the measurement of heme oxygenase-1 (HO-1) expression by reverse transcription-polymerase chain reaction (RT-qPCR), and western blot were performed on the SH-SY5Y cells induced by Ab25-35 in response to the treatment with genistein. Moreover, PI3K p85 phosphorylation was measured. RESULTS: Genistein enhanced the HO-1expression at both the mRNA and protein levels, as well as the PI3K p85 phosphorylation level. In addition, genistein increased the survival of SH-SY5Y cells treated with Ab25-35via HO-1 signaling. However, following transfection with Nrf2 small interfering RNA (siRNA) and treatment with LY294002, an inhibitor of PI3K p85, genistein could not upregulate HO-1 to exert neuroprotective effects on SH-SY5Y cells treated with Ab25-35. CONCLUSIONS: These results suggest that genistein exerts a neuroprotective effect on SH-SY5Y cells in vitro via Nrf2/ HO-1/PI3K signaling, providing a foundation for the application of genistein in the treatment of neurodegenerative diseases related to Nrf2/HO-1/PI3K signaling. FAU - Yi, Shanqing AU - Yi S AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Chen, Shuangxi AU - Chen S AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Xiang, Jian AU - Xiang J AD - Second People's Hospital of Shaoyang City, Shaoyang, Hunan 422001, PR China. FAU - Tan, Jian AU - Tan J AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Huang, Kailiang AU - Huang K AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Zhang, Hao AU - Zhang H AD - The Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Wang, Yilin AU - Wang Y AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. AD - The Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, PR China. FAU - Wu, Heng AU - Wu H AD - The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, PR China. c137001106@163.com. LA - eng PT - Journal Article DEP - 20210219 PL - Poland TA - Folia Histochem Cytobiol JT - Folia histochemica et cytobiologica JID - 8502651 RN - 0 (Amyloid beta-Peptides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Neuroprotective Agents) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (25-35)) RN - DH2M523P0H (Genistein) RN - EC 2.7.1.- (PIK3R1 protein, human) RN - EC 2.7.1.137 (Class Ia Phosphatidylinositol 3-Kinase) SB - IM MH - Alzheimer Disease/chemically induced/*drug therapy MH - Amyloid beta-Peptides MH - Apoptosis/drug effects MH - Cell Line, Tumor MH - Class Ia Phosphatidylinositol 3-Kinase/metabolism MH - Genistein/*pharmacology MH - Humans MH - NF-E2-Related Factor 2/metabolism MH - Neuroprotective Agents/*pharmacology MH - Peptide Fragments MH - Signal Transduction/*drug effects OTO - NOTNLM OT - Alzheimer's disease OT - Nrf2 OT - Nrf2/HO-1/PI3K pathway OT - SH-SY5Y cells OT - amyloid b25-35 OT - genistein OT - heme oxygenase-1 OT - in vitro OT - siRNA EDAT- 2021/02/20 06:00 MHDA- 2021/08/31 06:00 CRDT- 2021/02/19 08:40 PHST- 2020/12/17 00:00 [received] PHST- 2021/02/09 00:00 [accepted] PHST- 2021/02/04 00:00 [revised] PHST- 2021/02/20 06:00 [pubmed] PHST- 2021/08/31 06:00 [medline] PHST- 2021/02/19 08:40 [entrez] AID - VM/OJS/J/72393 [pii] AID - 10.5603/FHC.a2021.0006 [doi] PST - ppublish SO - Folia Histochem Cytobiol. 2021;59(1):49-56. doi: 10.5603/FHC.a2021.0006. Epub 2021 Feb 19.