Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice : Involvement of antioxidant potential
Copyright © 2023 Elsevier Ltd. All rights reserved..
Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:178 |
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| Enthalten in: |
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association - 178(2023) vom: 01. Aug., Seite 113869 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tran, Ngoc Kim Cuong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.08.2023 Date Revised 02.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.fct.2023.113869 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM358097584 |
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| 245 | 1 | 0 | |a Ginsenoside Re blocks Bay k-8644-induced neurotoxicity via attenuating mitochondrial dysfunction and PKCδ activation in the hippocampus of mice |b Involvement of antioxidant potential |
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| 500 | |a Date Revised 02.08.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a Although the anticonvulsant effects of ginsenosides are recognized, little is known about their effects on the convulsive behaviors induced by the activation of L-type Ca2+ channels. Here, we investigated whether ginsenoside Re (GRe) modulates excitotoxicity induced by the L-type Ca2+ channel activator Bay k-8644. GRe significantly attenuated Bay k-8644-induced convulsive behaviors and hippocampal oxidative stress in mice. GRe-mediated antioxidant potential was more pronounced in the mitochondrial fraction than cytosolic fraction. As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. GRe attenuated Bay k-8644-induced mitochondrial dysfunction, PKCδ activation, and neuronal loss. The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. Consistently, the GRe-mediated PKCδ inhibition and neuroprotection were counteracted by the mitochondrial toxin 3-nitropropionic acid or the PKC activator bryostatin-1. GRe treatment did not have additional effects on PKCδ gene knockout-mediated neuroprotection, suggesting that PKCδ is a molecular target of GRe. Collectively, our results suggest that GRe-mediated anticonvulsive/neuroprotective effects require the attenuation of mitochondrial dysfunction and altered redox status and inactivation of PKCδ | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Convulsive neurotoxicity | |
| 650 | 4 | |a Ginsenoside Re | |
| 650 | 4 | |a L-type calcium channel activator Bay k-8644 | |
| 650 | 4 | |a Mitochondrial dysfunction with altered redox status | |
| 650 | 4 | |a Mouse hippocampus | |
| 650 | 4 | |a Protein kinase Cδ gene | |
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| 700 | 1 | |a Jeong, Ji Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Naveen |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Yen Nhi Doan |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Hoang-Yen Phi |e verfasserin |4 aut | |
| 700 | 1 | |a Dang, Duy-Khanh |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jung Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Byun, Jae Kyung |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Dezhong |e verfasserin |4 aut | |
| 700 | 1 | |a Xiaoyan, Zeng |e verfasserin |4 aut | |
| 700 | 1 | |a Ko, Sung Kwon |e verfasserin |4 aut | |
| 700 | 1 | |a Nah, Seung-Yeol |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyoung-Chun |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Eun-Joo |e verfasserin |4 aut | |
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