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P4‐387: Valproic acid prevents hemin toxicity through HO‐1 downregulation by regulating a ubiquitin‐proteosomal pathway
Author(s) -
Moon Yeonsil,
Kwon Kyong Ja,
Shin Chan Young,
Han SeolHeui
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.09.201
Subject(s) - hemin , viability assay , chemistry , downregulation and upregulation , blot , wnt signaling pathway , heme oxygenase , mtt assay , neuroprotection , microbiology and biotechnology , signal transduction , pharmacology , cell growth , biochemistry , heme , biology , enzyme , cell , gene
Curcumin (0, 1.25, 5.0, 20mmol/L) for 24h. PC12 ischemic cell models were divided into 9 groups. Nrf-2 siRNA or empty plasmid was transiently transfected in PC12 cells by LipofectaminTM2000, and then the cells were treated for 24h. The protein expression of PI3K, AKT, Nrf-2 and HO-1 were detected by Western Blot. Results: Curcumin significantly improved the spatial learning and memory in the hippocampus CA1 area. The level of MDA decreased, but the activity of SOD increased, and the changes were in a dose-dependent manner (p <0.05). In the hippocampus the levels of PI3K, AKT, Nrf-2 and HO-1 protein significantly increased after treated with Curcumin. Immunohistochemistry results not only confirmed the above changes, but also displayed that Nrf-2 had translocated into the nuclear gradually with the increased dosage of Curcumin. In vitro the levels of the active oxygen decreased in PC12 cells after treated with Curcumin, and the changes were in a dose-dependent manner (p <0.05).The protein levels of PI3K, AKT, Nrf-2 and HO-1 increased in Curcumin group, whereas, they decreased or vanished after treated with Nrf-2 siRNA or LY294002. Conclusions: Curcumin has obviously neuroprotective effect on vascular dementia induced by chronic cerebral ischemia and can inhibit oxidative stress. The neuroprotective effect of Curcumin involved in activating PI3K/AKT/Nrf-2/HO-1 signaling pathway, and then promoting Nrf-2 transfer to the nuclear, increasing the protein levels of downstream product HO-1, and inhibiting oxidative stress induced by ischemia.