DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway
Oxidative stress in the brain is highly related to the pathogenesis of Alzheimer’s disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aβ) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid...
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MDPI AG
2022-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/9/1794 |
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| author | Yunhui Cai Ran Xiao Yadan Zhang Diya Xu Ni Wang Mengze Han Yili Zhang Lin Zhang Wenhua Zhou |
| author_facet | Yunhui Cai Ran Xiao Yadan Zhang Diya Xu Ni Wang Mengze Han Yili Zhang Lin Zhang Wenhua Zhou |
| author_sort | Yunhui Cai |
| collection | DOAJ |
| description | Oxidative stress in the brain is highly related to the pathogenesis of Alzheimer’s disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aβ) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid (AA) and O<sub>2</sub>. In this study, the protective effect of 5-hydroxy-7-(4′-hydroxy-3′-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on Aβ<sub>(1–42)</sub>/Cu<sup>2+</sup>/AA mixture-treated SH-SY5Y cells was investigated via in vitro and in silico studies. The results showed that DHPA could inhibit Aβ/Cu<sup>2+</sup>/AA-induced SH-SY5Y apoptosis, OH· production, intracellular ROS accumulation, and malondialdehyde (MDA) production. Further research demonstrated that DHPA could decrease the ratio of Bax/Bcl-2 and repress the increase of mitochondrial membrane potential (MMP) of SH-SY5Y cells, to further suppress the activation of caspase-3, and inhibit cell apoptosis. Meanwhile, DHPA could inhibit the Aβ/Cu<sup>2+</sup>/AA-induced phosphorylation of Erk1/2 and P38 in SH-SY5Y cells, and increase the expression of P-AKT. Furthermore, DHPA could bind to Keap1 to promote the separation of Nrf2 to Keap1 and activate the Keap1/Nrf2/HO-1 signaling pathway to increase the expression of heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO1), glutathione (GSH), and superoxide dismutase (SOD). Thus, our results demonstrated that DHPA could inhibit Aβ/Cu<sup>2+</sup>/AA-induced SH-SY5Y apoptosis via scavenging OH·, inhibit mitochondria apoptosis, and activate the Keap1/Nrf2/HO-1 signaling pathway. |
| first_indexed | 2024-03-10T00:52:49Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T00:52:49Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-5c1bed52f3444f208d040a13d175c6bd2023-11-23T14:49:00ZengMDPI AGAntioxidants2076-39212022-09-01119179410.3390/antiox11091794DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling PathwayYunhui Cai0Ran Xiao1Yadan Zhang2Diya Xu3Ni Wang4Mengze Han5Yili Zhang6Lin Zhang7Wenhua Zhou8Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaHunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, ChinaOxidative stress in the brain is highly related to the pathogenesis of Alzheimer’s disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aβ) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid (AA) and O<sub>2</sub>. In this study, the protective effect of 5-hydroxy-7-(4′-hydroxy-3′-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on Aβ<sub>(1–42)</sub>/Cu<sup>2+</sup>/AA mixture-treated SH-SY5Y cells was investigated via in vitro and in silico studies. The results showed that DHPA could inhibit Aβ/Cu<sup>2+</sup>/AA-induced SH-SY5Y apoptosis, OH· production, intracellular ROS accumulation, and malondialdehyde (MDA) production. Further research demonstrated that DHPA could decrease the ratio of Bax/Bcl-2 and repress the increase of mitochondrial membrane potential (MMP) of SH-SY5Y cells, to further suppress the activation of caspase-3, and inhibit cell apoptosis. Meanwhile, DHPA could inhibit the Aβ/Cu<sup>2+</sup>/AA-induced phosphorylation of Erk1/2 and P38 in SH-SY5Y cells, and increase the expression of P-AKT. Furthermore, DHPA could bind to Keap1 to promote the separation of Nrf2 to Keap1 and activate the Keap1/Nrf2/HO-1 signaling pathway to increase the expression of heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO1), glutathione (GSH), and superoxide dismutase (SOD). Thus, our results demonstrated that DHPA could inhibit Aβ/Cu<sup>2+</sup>/AA-induced SH-SY5Y apoptosis via scavenging OH·, inhibit mitochondria apoptosis, and activate the Keap1/Nrf2/HO-1 signaling pathway.https://www.mdpi.com/2076-3921/11/9/1794Alzheimer’s diseaseoxidative stressSH-SY5Y cellmitochondriaNrf2ROS |
| spellingShingle | Yunhui Cai Ran Xiao Yadan Zhang Diya Xu Ni Wang Mengze Han Yili Zhang Lin Zhang Wenhua Zhou DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway Antioxidants Alzheimer’s disease oxidative stress SH-SY5Y cell mitochondria Nrf2 ROS |
| title | DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_full | DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_fullStr | DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_full_unstemmed | DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_short | DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway |
| title_sort | dhpa protects sh sy5y cells from oxidative stress induced apoptosis via mitochondria apoptosis and the keap1 nrf2 ho 1 signaling pathway |
| topic | Alzheimer’s disease oxidative stress SH-SY5Y cell mitochondria Nrf2 ROS |
| url | https://www.mdpi.com/2076-3921/11/9/1794 |
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