Ucf-101 protects in vivoandin vitro models of PD against 6-hydroxydopamine toxicity by alleviating endoplasmic reticulum stress via the Wnt/β-catenin pathway
Copyright © 2019 Elsevier Ltd. All rights reserved..
The accumulation of α-syn which induce endoplasmic reticulum stress (ERS) and mediate various signaling pathways involved in DA neuronal degeneration, and the apoptosis of dopamine (DA) neurons are pathological markers of Parkinson's disease (PD). High-temperature requirement protein A2 (HtrA2) is synthesized in the endoplasmic reticulum, and the expression level of HtrA2 can be upregulated by drugs or by unfolded proteins. Ucf-101 is a specific inhibitor of HtrA2, and studies have shown that Ucf-101 reduced apoptosis in PC12 cells. Our study showed that PC12 cells treated with 60 μM 6-OHDA for 24 h had significantly decreased cell viability compared to that of controls. A low concentration (2.5 μM) of Ucf-101 decreased the apoptosis rate of the PD cell model, but a high concentration (≥10 μM) increased the apoptosis rate, compared to that of controls. 6-OHDA upregulated the expression of HtrA2, α-syn, CHOP, Grp78 and active caspase-3 and reduced the levels of TH and XIAP. Ucf-101 reduced the level of ERS and apoptosis bothin vivoandin vitro. The ratio of p-GSK3β (Tyr216 to Ser9) increased in PD rats. However, Ucf-101 down-regulated the activation of GSK3β and activated the Wnt/β-catenin pathway that was caused by 6-OHDA. Ucf-101 activated the Wnt/β-catenin pathway and significantly attenuated 6-OHDA-induced neurotoxicity, which was related to the inhibition of ERS and the reduction of the apoptosis rate of PC12 cells and DA neurons in the midbrain of PD rats. Ucf-101 has certain neuroprotective effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia - 71(2020) vom: 05. Jan., Seite 217-225 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yanxia [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Completed 22.07.2020 Date Revised 22.07.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jocn.2019.11.023 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304838128 |
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| 520 | |a Copyright © 2019 Elsevier Ltd. All rights reserved. | ||
| 520 | |a The accumulation of α-syn which induce endoplasmic reticulum stress (ERS) and mediate various signaling pathways involved in DA neuronal degeneration, and the apoptosis of dopamine (DA) neurons are pathological markers of Parkinson's disease (PD). High-temperature requirement protein A2 (HtrA2) is synthesized in the endoplasmic reticulum, and the expression level of HtrA2 can be upregulated by drugs or by unfolded proteins. Ucf-101 is a specific inhibitor of HtrA2, and studies have shown that Ucf-101 reduced apoptosis in PC12 cells. Our study showed that PC12 cells treated with 60 μM 6-OHDA for 24 h had significantly decreased cell viability compared to that of controls. A low concentration (2.5 μM) of Ucf-101 decreased the apoptosis rate of the PD cell model, but a high concentration (≥10 μM) increased the apoptosis rate, compared to that of controls. 6-OHDA upregulated the expression of HtrA2, α-syn, CHOP, Grp78 and active caspase-3 and reduced the levels of TH and XIAP. Ucf-101 reduced the level of ERS and apoptosis bothin vivoandin vitro. The ratio of p-GSK3β (Tyr216 to Ser9) increased in PD rats. However, Ucf-101 down-regulated the activation of GSK3β and activated the Wnt/β-catenin pathway that was caused by 6-OHDA. Ucf-101 activated the Wnt/β-catenin pathway and significantly attenuated 6-OHDA-induced neurotoxicity, which was related to the inhibition of ERS and the reduction of the apoptosis rate of PC12 cells and DA neurons in the midbrain of PD rats. Ucf-101 has certain neuroprotective effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a ERS | |
| 650 | 4 | |a HtrA2 inhibitor | |
| 650 | 4 | |a Parkinson’s disease | |
| 650 | 4 | |a Ucf-101 | |
| 650 | 4 | |a Wnt/β-catenin | |
| 650 | 7 | |a Neuroprotective Agents |2 NLM | |
| 650 | 7 | |a Pyrimidinones |2 NLM | |
| 650 | 7 | |a Thiones |2 NLM | |
| 650 | 7 | |a UCF 101 |2 NLM | |
| 650 | 7 | |a beta Catenin |2 NLM | |
| 700 | 1 | |a Liu, Zhaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhengquan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuling |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Sen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ji |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xinling |e verfasserin |4 aut | |
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