ACS omega · 2025
Role of the PKA-PGC1α-BACE1 Signaling Pathway in Aluminum-Induced Neurotoxicity in PC12 Cells.
СтатьяНазвание и аннотация: Перевод в очереди
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Wang Ruo-Nan, Kong Fan-Peng, Wang Zhuo-Hui, Hu Wen-Cheng, Pei Zi-Yan, Song Jing, Lu Xiao-Ting, Pan Bao-Long
Аннотация
OBJECT: This objective of this study was to investigate how aluminum affects the PKA-PGC1α-BACE1 pathway in PC12 cells and its role in neurotoxicity.
METHOD: According to the exposure dose of aluminum maltol, PC12 cells were selected for research and divided into five experimental groups and six intervention groups. After 24 h of 8-Bromo-cAMP intervention, they were treated with Al-(mal)3 for 24 h. After the experiment, cell morphology was observed, and the cell survival rate was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot and ELISA techniques were used to detect the expression of relevant proteins, enzyme activity, and Aβ levels.
RESULT: Under the microscope, the number of cells in the aluminum maltol group decreased, the morphology changed, and the number of intercellular connections decreased. However, after treatment with the 8-Bromo-cAMP agonist, a significant increase in the number of cells was observed, and significant morphological changes occurred, with a gradual increase in intercellular connections. CCK-8 assays showed that cell viability gradually decreased with increasing aluminum exposure doses. Western blot showed that PKA and PGC1α expressions decreased with higher aluminum doses, while BACE1 increased; agonist treatment upregulated PGC1α and downregulated BACE1, with minimal effect on PKA; and ELISA results indicated that aluminum reduced PKA enzyme activity but increased BACE1 activity and Aβ levels.
CONCLUSION: Exposure to aluminum inhibits the PKA-PGC1α-BACE1 signaling pathway, while PKA agonists can alleviate neurotoxicity by restoring this pathway.
METHOD: According to the exposure dose of aluminum maltol, PC12 cells were selected for research and divided into five experimental groups and six intervention groups. After 24 h of 8-Bromo-cAMP intervention, they were treated with Al-(mal)3 for 24 h. After the experiment, cell morphology was observed, and the cell survival rate was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot and ELISA techniques were used to detect the expression of relevant proteins, enzyme activity, and Aβ levels.
RESULT: Under the microscope, the number of cells in the aluminum maltol group decreased, the morphology changed, and the number of intercellular connections decreased. However, after treatment with the 8-Bromo-cAMP agonist, a significant increase in the number of cells was observed, and significant morphological changes occurred, with a gradual increase in intercellular connections. CCK-8 assays showed that cell viability gradually decreased with increasing aluminum exposure doses. Western blot showed that PKA and PGC1α expressions decreased with higher aluminum doses, while BACE1 increased; agonist treatment upregulated PGC1α and downregulated BACE1, with minimal effect on PKA; and ELISA results indicated that aluminum reduced PKA enzyme activity but increased BACE1 activity and Aβ levels.
CONCLUSION: Exposure to aluminum inhibits the PKA-PGC1α-BACE1 signaling pathway, while PKA agonists can alleviate neurotoxicity by restoring this pathway.