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Increased glycogen synthase kinase 3β activity involves in the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 in HT22 cells / 中华神经科杂志
Chinese Journal of Neurology ; (12): 96-102, 2020.
Article in Chinese | WPRIM | ID: wpr-799509
ABSTRACT
Objective@#To investigate the effect of glycogen synthase kinase 3β (GSK3β) on the decreased expression of Bmal1 induced by amyloid-beta protein 31-35 (Aβ31-35) in HT22 cells.@*Methods@#HT22 mouse hippocampal cells were divided into control group, Aβ31-35 group and LiCl+Aβ 31-35 group by random number table method in the present study. Cells were synchronized to G0/G1 phase by 1% serum starvation for 1 hour (circadian time 0 (CT0)). Cell viability was detected by the cell counting kit-8 assay. The mRNA expression of clock gene Bmal1 was examined by real-time PCR at different CT times. The expression of GSK3β and BMAL1 protein was detected by Western blotting.@*Results@#Compared with the control group, Aβ31-35 induced the decreased expression of Bmal1 mRNA; The expression of both Bmal1 mRNA and BMAL1 protein was decreased significantly at CT20 (Bmal1 mRNA 0.38±0.06 vs 0.83±0.08, t=4.549, P=0.001; BMAL1 protein 0.67±0.04 vs 1.00±0.04, t=5.943, P<0.001). In the Aβ31-35 group, GSK3β activity was increased and the ratio of phosphorylated GSK3βS9 to GSK3β was decreased compared to the control group (0.66±0.08 vs 1.02±0.14, t=2.217, P=0.025). Aβ31-35 decreased the viability of HT22 cells (71.85%±6.20% in the Aβ31-35 group vs 98.14%±2.68% in the control group, t=3.891, P=0.006), and the GSK3β inhibitor LiCl pretreatment effectively reversed the decline of the viability induced by Aβ31-35 (90.74%±5.74% in the LiCl+Aβ31-35 group vs 71.85%±6.20% in the Aβ31-35 group, t=3.412, P=0.010). LiCl (in the LiCl+Aβ31-35 group) increased the expression of Bmal1 mRNA and BMAL1 protein significantly at CT20 compared with the Aβ31-35 group (Bmal1 mRNA 0.72±0.05 vs 0.38±0.06, t=4.378, P=0.001; BMAL1 protein 0.90±0.04 vs 0.67±0.04, t=4.052, P=0.002).@*Conclusion@#Increased GSK3β activity involved in the decreased expression of Bmal1 induced by Aβ31-35 in HT22 cells.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Neurology Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Neurology Year: 2020 Type: Article