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

Autor: LI Yan-ju, ZHANG Ge, WANG Xiao-jing, XING Xiao-min, MA Guo-zhao
Předmět:
Zdroj: Chinese Journal of Contemporary Neurology & Neurosurgery; Nov2021, Vol. 21 Issue 11, p942-950, 9p
Abstrakt: Objective To investigate the potential signal transduction mechanism of β-amyloid protein 1-42 (Aβ1-42) induced up-regulation of ATP sensitive potassium channel KATP 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 - kB (NF-kB) 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 Aβ1-42 (30 min later), respectively. Western blotting was used to detect the protein expression of KATP subunit SUR1/Kir6.2 after 72 h of culture. Results 1) NF-kB inhibitor SN50: SUR1/Kir6.2 proteins of KATP subunit in SN50 + Aβ1-42 group were lower than that in control group (t = 6.237, P = 0.010; t = 7.136, P = 0.004) and Aβ1-42 group (t = 12.620, P = 0.000; t = 18.580, P = 0.000), but the SUR1 protein expression of KATP subunit in SN50 + Aβ1-42 group was higher than that in SN50 group (t = 6.002, P = 0.012). SUR1/Kir6.2 proteins of KATP subunit in SN50 group were lower than that in control group (t = 12.240, P = 0.000; t = 4.906, P = 0.034) and Aβ1-42 group (t = 18.620, P = 0.000; t = 16.350, P = 0.000). 2) p38 MAPK inhibitor SB203580: the proteins expression of KATP subunit SUR1/Kir6.2 in SB203580 + Aβ1-42 group were lower than that in Aβ1-42 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 KATP subunit Kir6.2 protein in SB203580 + Aβ1-42 group was higher than that in control group (t = 7.537, P = 0.003). The SUR1/Kir6.2 proteins expression of KATP subunit in SB203580 group were lower than that in control group (t = 8.089, P = 0.002; t = 19.380, P = 0.003) and Aβ1-42 group (t = 18.870, P = 0.000; t = 35.430, P = 0.000). 3) PKC inhibitor CTC: the SUR1 protein expression of KATP subunit in CTC + Aβ1-42 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 Aβ1-42 group (t = 15.170, P = 0.000). The SUR1 protein expression of KATP subunit in CTC group was lower than that in control group (t = 24.000, P = 0.000), Aβ1-42 group (t = 43.930, P = 0.000) and CTC + Aβ1-42 group. The protein expression of KATP subunit Kir6.2 in CTC + Aβ1-42 group was lower than that in control group (t = 15.000, P = 0.000), Aβ1-42 group (t = 24.140, P = 0.000) and CTC group (t = 5.571, P = 0.018). The expression of KATP subunit Kir6.2 protein in CTC group was lower than that in control group (t = 9.429, P = 0.001) and in Aβ1-42 group (t = 18.570, P = 0.000). Conclusions NF-kB, p38 MAPK and PKC signaling pathways are involved in Aβ1-42 up-regulation of SUR1/Kir6.2 proteins expression of KATP subunit in cortical and hippocampal neurons of rats. [ABSTRACT FROM AUTHOR]
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