Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death
Natural sources are very promising materials for the discovery of novel bioactive compounds with diverse pharmacological effects. In recent years, many researchers have focused on natural sources as a means to prevent neuronal cell death in neuropathological conditions. This study focused on identif...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/20/1/142 |
| _version_ | 1811325795760603136 |
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| author | Ji Hoon Song Hae-Jeung Lee Ki Sung Kang |
| author_facet | Ji Hoon Song Hae-Jeung Lee Ki Sung Kang |
| author_sort | Ji Hoon Song |
| collection | DOAJ |
| description | Natural sources are very promising materials for the discovery of novel bioactive compounds with diverse pharmacological effects. In recent years, many researchers have focused on natural sources as a means to prevent neuronal cell death in neuropathological conditions. This study focused on identifying neuroprotective compounds and their underlying molecular mechanisms. Procyanidin C1 (PC-1) was isolated from grape seeds and assessed for biological effects against glutamate-induced HT22 cell death. The results showed that PC-1 strongly prevented glutamate-induced HT22 cell death. Moreover, PC-1 was also found to prevent glutamate-induced chromatin condensation and reduce the number of annexin V-positive cells indicating apoptotic cell death. Procyanidin C1 possessed a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and inhibited glutamate-induced accumulation of intracellular reactive oxygen species and protein carbonylation. Additionally, PC-1 mediated nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 and increased the expression levels of heme oxygenase (HO-1). Inhibition of HO-1 by tin protoporphyrin, a synthetic inhibitor, reduced the protective effect of PC-1. Furthermore, PC-1 also blocked glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38, but not JNK. This study is the first experimental report to demonstrate the neuroprotective effects of PC-1 against glutamate-induced cytotoxicity in HT22 cells. Therefore, our results suggest that PC-1, as a potent bioactive compound of grape seeds, can prevent neuronal cell death in neuropathological conditions. |
| first_indexed | 2024-04-13T14:39:12Z |
| format | Article |
| id | doaj.art-cece662cd49445c5bbc3122eb0418a64 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T14:39:12Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cece662cd49445c5bbc3122eb0418a642022-12-22T02:42:57ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-01-0120114210.3390/ijms20010142ijms20010142Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell DeathJi Hoon Song0Hae-Jeung Lee1Ki Sung Kang2College of Korean Medicine, Gachon University, Seongnam 13120, KoreaCollege of Bio-Nano Technology, Department of Food and Nutrition, Gachon University, Seongnam 13120, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaNatural sources are very promising materials for the discovery of novel bioactive compounds with diverse pharmacological effects. In recent years, many researchers have focused on natural sources as a means to prevent neuronal cell death in neuropathological conditions. This study focused on identifying neuroprotective compounds and their underlying molecular mechanisms. Procyanidin C1 (PC-1) was isolated from grape seeds and assessed for biological effects against glutamate-induced HT22 cell death. The results showed that PC-1 strongly prevented glutamate-induced HT22 cell death. Moreover, PC-1 was also found to prevent glutamate-induced chromatin condensation and reduce the number of annexin V-positive cells indicating apoptotic cell death. Procyanidin C1 possessed a strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and inhibited glutamate-induced accumulation of intracellular reactive oxygen species and protein carbonylation. Additionally, PC-1 mediated nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 and increased the expression levels of heme oxygenase (HO-1). Inhibition of HO-1 by tin protoporphyrin, a synthetic inhibitor, reduced the protective effect of PC-1. Furthermore, PC-1 also blocked glutamate-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2 and p38, but not JNK. This study is the first experimental report to demonstrate the neuroprotective effects of PC-1 against glutamate-induced cytotoxicity in HT22 cells. Therefore, our results suggest that PC-1, as a potent bioactive compound of grape seeds, can prevent neuronal cell death in neuropathological conditions.http://www.mdpi.com/1422-0067/20/1/142procyanidin C1glutamateoxidative stressNrf2/HO-1 signaling pathwayMAPKneuroprotective effects |
| spellingShingle | Ji Hoon Song Hae-Jeung Lee Ki Sung Kang Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death International Journal of Molecular Sciences procyanidin C1 glutamate oxidative stress Nrf2/HO-1 signaling pathway MAPK neuroprotective effects |
| title | Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death |
| title_full | Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death |
| title_fullStr | Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death |
| title_full_unstemmed | Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death |
| title_short | Procyanidin C1 Activates the Nrf2/HO-1 Signaling Pathway to Prevent Glutamate-Induced Apoptotic HT22 Cell Death |
| title_sort | procyanidin c1 activates the nrf2 ho 1 signaling pathway to prevent glutamate induced apoptotic ht22 cell death |
| topic | procyanidin C1 glutamate oxidative stress Nrf2/HO-1 signaling pathway MAPK neuroprotective effects |
| url | http://www.mdpi.com/1422-0067/20/1/142 |
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