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Protective Effect of YC-1 Against ADDLs-induced Toxicity and HIF-1α Related Mechanism

YAN Peng;QIAO Xian;LIU Jin-ling;SUN Sheng-gang;ZHENG Jin;Department of Neurology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology;  
Objective:To study the protective effect of YC-1 against ADDLs(Aβ oligomers)-induced toxicity and related mechanism. Methods: Different concentrations(500 nmol/L, 1 μmol/L, 2 μmol/L, 5 μmol/L, 10 μmol/L, 20 μmol/L) of ADDLs were used to intervene the primary co-culture system of mouse cortical neurons and astrocytes, and YC-1 was applied at the same time. CCK-8 assays were used to assess cell vitality of co-culture cells. NICD and HIF-1α levels of primary co-culture system were assessed with western blot, and real-time PCR was used to detect apoptosis associated Caspase-3 mRNA level of co-culture system. Results: ADDLs at ≥2 μmol/L reduced the cell viability of the co-culture system in a concentration-dependent manner(P0.01). Exposure to 10 μmol/L ADDLs for 4 hours showed obvious toxic effect on the co-culture system(P 0.01), while the application of YC-1 significantly attenuated the toxic effect induced by ADDLs(P0.01). The NICD and HIF-1α levels were up-regulated after the exposure of 10 μmol/L ADDLs for 4 hours(P0.01), while the application of YC-1 significantly attenuated the up-regulation of the protein levels(P0.05 or 0.01). The Caspase-3 mRNA level was increased after intervened by 10 μmol/L ADDLs for 4 hours(P0.01), and YC-1 significantly inhibited the increase(P 0.05). Conclusion: The toxic effect induced by ADDLs on primary co-culture system of mouse cortical neurons and astrocytes could be protected by YC-1.
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