The effect of signal pathways on the neural KATP subunits SUR1/Kir6.2 expression induced by Aβ1-42

Abstract

Objective To investigate the potential signal transduction mechanism of β⁃amyloid protein 1-42 (Aβ_1-42) induced up⁃regulation of ATP sensitive potassium channel K_ATP subunit SUR1/Kir6.2 proteins expression. Methods The primary cultured cortical and hippocampal neurons of rats were identified by immunocytochemistry. The experimental groups were added with 0.50 μmol/L nuclear factor⁃κB (NF⁃κB) inhibitor SN50, 2 μmol/L p38 mitogen⁃activated protein kinase (MAPK) inhibitor SB203580 or 2 μmol/L protein kinease C (PKC) inhibitor CTC, 2 μmol/L Aβ_1-42 (30 min later), respectively. Western blotting was used to detect the protein expression of K_ATP subunit SUR1/Kir6.2 after 72 h of culture. Results 1) NF⁃κB inhibitor SN50: SUR1/Kir6.2 proteins of K_ATP subunit in SN50+Aβ_1-42 group were lower than that in control group (t=6.237, P=0.010; t=7.136, P=0.004) and Aβ_1-42 group (t=12.620, P=0.000; t=18.580, P=0.000), but the SUR1 protein expression of K_ATP subunit in SN50+Aβ_1-42 group was higher than that in SN50 group (t=6.002, P=0.012). SUR1/Kir6.2 proteins of K_ATP subunit in SN50 group were lower than that in control group (t=12.240, P=0.000; t=4.906, P=0.034) and Aβ_1-42 group (t=18.620, P=0.000; t=16.350, P=0.000). 2) p38 MAPK inhibitor SB203580: the proteins expression of K_ATP subunit SUR1/Kir6.2 in SB203580+Aβ_1-42 group were lower than that in Aβ_1-42 group (t=13.010, P=0.000; t=8.506, P=0.001), but higher than that in SB203580 group (t=5.869, P=0.014; t=26.920, P=0.000), but the expression of K_ATP subunit Kir6.2 protein in SB203580+Aβ_1-42 group was higher than that in control group (t=7.537, P=0.003). The SUR1/Kir6.2 proteins expression of K_ATP subunit in SB203580 group were lower than that in control group (t=8.089, P=0.002; t=19.380, P=0.003) and Aβ_1-42 group (t=18.870, P=0.000; t=35.430, P=0.000). 3) PKC inhibitor CTC: the SUR1 protein expression of K_ATP subunit in CTC+Aβ_1-42 group was higher than that in control group (t=4.756, P=0.040) and in CTC group (t=28.760, P=0.000), but lower than that in Aβ_1-42 group (t=15.170, P=0.000). The SUR1 protein expression of K_ATP subunit in CTC group was lower than that in control group (t=24.000, P=0.000), Aβ_1-42 group (t=43.930, P=0.000) and CTC+Aβ_1-42 group. The protein expression of K_ATP subunit Kir6.2 in CTC+Aβ_1-42 group was lower than that in control group (t=15.000, P=0.000), Aβ_1-42 group (t=24.140, P=0.000) and CTC group (t=5.571, P=0.018). The expression of K_ATP subunit Kir6.2 protein in CTC group was lower than that in control group (t=9.429, P=0.001) and in Aβ_1-42 group (t=18.570, P=0.000). Conclusions NF⁃κB, p38 MAPK and PKC signaling pathways are involved in Aβ_1-42 up⁃regulation of SUR1/Kir6.2 proteins expression of K_ATP subunit in cortical and hippocampal neurons of rats.

doi：10.3969/j.issn.1672⁃6731.2021.11.005