The effect of signal pathways on the neural KATP subunits SUR1/Kir6.2 expression induced by A&beta;1-42

doi:10.3969/j.issn.1672-6731.2021.11.005

Abstract

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.

Key words: Amyloid beta-peptides, Potassium channels, NF-kappa B, p38 mitogen-activated protein kinases, Protein kinase C, Blotting, western, Cells, cultured

摘要：

目的分析探讨β-淀粉样蛋白1~42（Aβ_1~42）诱导ATP敏感性钾离子通道（K_ATP）亚基SUR1/Kir6.2蛋白表达上调的潜在信号转导机制。方法采用免疫细胞化学法鉴定原代培养的大鼠皮质和海马神经元，实验组分别加入0.50 μmol/L核因子-κB（NF-κB）抑制剂SN50、2 μmol/L p38丝裂原激活蛋白激酶（MAPK）抑制剂SB203580或者2 μmol/L蛋白激酶C（PKC）抑制剂CTC，于30 min后分别加入2 μmol/L Aβ_1~42，培养72 h后采用Western blotting法检测K_ATP亚基SUR1/Kir6.2蛋白的相对表达量。结果（1）NF-κB抑制剂SN50：SN50+Aβ_1~42组SUR1/Kir6.2蛋白表达量低于对照组（t=6.237，P=0.010；t=7.136，P=0.004）和Aβ_1~42组（t=12.620，P=0.000；t=18.580，P=0.000），SN50组SUR1/Kir6.2蛋白相对表达量低于对照组（t=12.240，P=0.000；t=4.906，P=0.034）、Aβ_1~42组（t=18.620，P=0.000；t=16.350，P=0.000）和SN50+Aβ_1~42组（t=6.002，P=0.012）。（2）p38 MAPK抑制剂SB203580：SB203580+Aβ_1~42组SUR1/Kir6.2蛋白相对表达量低于Aβ_1~42组（t=13.010，P=0.000；t=8.506，P=0.001），仅Kir6.2蛋白相对表达量高于对照组（t=7.537，P=0.003）；SB203580组SUR1/Kir6.2蛋白相对表达量低于对照组（t=8.089，P=0.002；t=19.380，P=0.000）、Aβ_1~42组（t=18.870，P=0.000；t=35.430，P=0.000）和SB203580+Aβ_1~42组（t=5.869，P=0.014；t=26.920，P=0.000）。（3）PKC抑制剂CTC：CTC+Aβ_1~42组SUR1蛋白相对表达量高于对照组（t=4.756，P=0.040）、但低于Aβ_1~42组（t=15.170，P=0.000），CTC组SUR1蛋白相对表达量低于对照组（t=24.000，P=0.000）、Aβ_1~42组（t=43.930，P=0.000）和CTC+Aβ_1~42组（t=28.760，P=0.000）；CTC+Aβ_1~42组Kir6.2蛋白相对表达量低于对照组（t=15.000，P=0.000）和Aβ_1~42组（t=24.140，P=0.000），CTC组Kir6.2蛋白相对表达量低于对照组（t=9.429，P=0.001）和Aβ_1~42组（t=18.570，P=0.000）、但高于CTC+Aβ_1~42组（t=5.571，P=0.018）。结论 NF-κB、p38 MAPK和PKC信号转导通路参与Aβ_1~42上调大鼠皮质和海马神经元K_ATP亚基SUR1/Kir6.2蛋白的表达。

关键词: 淀粉样β肽类, 钾通道, NF-κB, p38丝裂原活化蛋白激酶类, 蛋白激酶C, 印迹法,蛋白质, 细胞,培养的

LI Yan-ju, ZHANG Ge, WANG Xiao-jing, XING Xiao-min, MA Guo-zhao. The effect of signal pathways on the neural K_ATP subunits SUR1/Kir6.2 expression induced by Aβ_1-42[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2021, 21(11): 942-950.

李艳菊, 张戈, 王晓静, 邢孝民, 马国诏. Aβ_1~42诱导K_ATP亚基SUR1/Kir6.2蛋白表达的信号转导通路研究[J]. 中国现代神经疾病杂志, 2021, 21(11): 942-950.

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URL: https://journal11.magtechjournal.com/cjcnn/EN/10.3969/j.issn.1672-6731.2021.11.005

https://journal11.magtechjournal.com/cjcnn/EN/Y2021/V21/I11/942

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The effect of signal pathways on the neural K_ATP subunits SUR1/Kir6.2 expression induced by Aβ_1-42

Aβ_1~42诱导K_ATP亚基SUR1/Kir6.2蛋白表达的信号转导通路研究

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

Aβ1~42诱导KATP亚基SUR1/Kir6.2蛋白表达的信号转导通路研究

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The effect of signal pathways on the neural K_ATP subunits SUR1/Kir6.2 expression induced by Aβ_1-42

Aβ_1~42诱导K_ATP亚基SUR1/Kir6.2蛋白表达的信号转导通路研究