Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway
The effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent...
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2022-01-01
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author | Jiwon Ko Soyoung Jang Wookbong Kwon Si-Yong Kim Soyeon Jang Eungyung Kim Young-Rae Ji Sijun Park Myoung-Ok Kim Seong-Kyoon Choi Dong-Hyung Cho Hyun-Shik Lee Su-Geun Lim Zae-Young Ryoo |
author_facet | Jiwon Ko Soyoung Jang Wookbong Kwon Si-Yong Kim Soyeon Jang Eungyung Kim Young-Rae Ji Sijun Park Myoung-Ok Kim Seong-Kyoon Choi Dong-Hyung Cho Hyun-Shik Lee Su-Geun Lim Zae-Young Ryoo |
author_sort | Jiwon Ko |
collection | DOAJ |
description | The effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent manner, intracellular ROS were excessively generated, and additional cell damage occurred in the form of lipid peroxidation. The neurotoxicity caused by excessive glutamate was found to be ferroptosis and not apoptosis. Other factors (GPx-4, Nrf2, Nox1 and Hspb1) involved in ferroptosis were also identified. In other words, it was confirmed that GIP increased the activity of sub-signalling molecules in the process of suppressing ferroptosis as an antioxidant and maintained a stable cell cycle even under glutamate-induced neurotoxicity. At the same time, in HT-22 cells exposed to ferroptosis as a result of excessive glutamate accumulation, GIP sustained cell viability by activating the mitogen-activated protein kinase (MAPK) signalling pathway. These results suggest that the overexpression of the GIP gene increases cell viability by regulating mechanisms related to cytotoxicity and reactive oxygen species production in hippocampal neuronal cell lines. |
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id | doaj.art-bddcef9aefec4d7c85ade52fe497cf66 |
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language | English |
last_indexed | 2024-03-09T22:45:48Z |
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spelling | doaj.art-bddcef9aefec4d7c85ade52fe497cf662023-11-23T18:29:48ZengMDPI AGAntioxidants2076-39212022-01-0111218910.3390/antiox11020189Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling PathwayJiwon Ko0Soyoung Jang1Wookbong Kwon2Si-Yong Kim3Soyeon Jang4Eungyung Kim5Young-Rae Ji6Sijun Park7Myoung-Ok Kim8Seong-Kyoon Choi9Dong-Hyung Cho10Hyun-Shik Lee11Su-Geun Lim12Zae-Young Ryoo13BK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaCore Protein Resources Center, DGIST, Daegu 42988, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaDepartment of Animal Science and Biotechnology, Kyungpook National University, Sangju-si 37224, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, Kyungpook National University, Daegu 42988, KoreaDepartment of Animal Science and Biotechnology, Kyungpook National University, Sangju-si 37224, KoreaCore Protein Resources Center, DGIST, Daegu 42988, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaSchool of Life Science, Kyungpook National University, Daegu 42988, KoreaBK21 FOUR KNU Creative BioResearch Group, School of Life Sciences, Kyungpook National University, Daegu 41566, KoreaThe effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent manner, intracellular ROS were excessively generated, and additional cell damage occurred in the form of lipid peroxidation. The neurotoxicity caused by excessive glutamate was found to be ferroptosis and not apoptosis. Other factors (GPx-4, Nrf2, Nox1 and Hspb1) involved in ferroptosis were also identified. In other words, it was confirmed that GIP increased the activity of sub-signalling molecules in the process of suppressing ferroptosis as an antioxidant and maintained a stable cell cycle even under glutamate-induced neurotoxicity. At the same time, in HT-22 cells exposed to ferroptosis as a result of excessive glutamate accumulation, GIP sustained cell viability by activating the mitogen-activated protein kinase (MAPK) signalling pathway. These results suggest that the overexpression of the GIP gene increases cell viability by regulating mechanisms related to cytotoxicity and reactive oxygen species production in hippocampal neuronal cell lines.https://www.mdpi.com/2076-3921/11/2/189monosodium glutamateneurotoxicityferroptosisoxidative stresscellular oxidative homeostasismouse hippocampal HT-22 cells |
spellingShingle | Jiwon Ko Soyoung Jang Wookbong Kwon Si-Yong Kim Soyeon Jang Eungyung Kim Young-Rae Ji Sijun Park Myoung-Ok Kim Seong-Kyoon Choi Dong-Hyung Cho Hyun-Shik Lee Su-Geun Lim Zae-Young Ryoo Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway Antioxidants monosodium glutamate neurotoxicity ferroptosis oxidative stress cellular oxidative homeostasis mouse hippocampal HT-22 cells |
title | Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway |
title_full | Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway |
title_fullStr | Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway |
title_full_unstemmed | Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway |
title_short | Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway |
title_sort | protective effect of gip against monosodium glutamate induced ferroptosis in mouse hippocampal ht 22 cells through the mapk signaling pathway |
topic | monosodium glutamate neurotoxicity ferroptosis oxidative stress cellular oxidative homeostasis mouse hippocampal HT-22 cells |
url | https://www.mdpi.com/2076-3921/11/2/189 |
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