Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells
Glutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/5/1090 |
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| author | Yoshiaki Uchida Farhana Ferdousi Shinya Takahashi Hiroko Isoda |
| author_facet | Yoshiaki Uchida Farhana Ferdousi Shinya Takahashi Hiroko Isoda |
| author_sort | Yoshiaki Uchida |
| collection | DOAJ |
| description | Glutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events regulated by GSH under physiological and oxidative stress conditions has also not been reported. In this study, DNA microarray analysis was performed with four experiment arms including Control, GSH, hydrogen peroxide (HP), and GSH + HP treatment groups. The GSH-treated group exhibited a significant upregulation of genes clustered in cell proliferation, growth, and differentiation, particularly those related to MAPK, when compared with the Control group. Additionally, liver functions such as alcohol and cholesterol metabolic processes were significantly upregulated. On the other hand, in the HP-induced oxidative stress condition, GSH (GSH + HP group) demonstrated a significant activation of cell proliferation, cell cycle, and various signalling pathways (including TGFβ, MAPK, PI3K/AKT, and HIF-1) in comparison to the HP group. Furthermore, several disease-related pathways, such as chemical carcinogenesis–reactive oxygen species and fibrosis, were significantly downregulated in the GSH + HP group compared to the HP group. Collectively, our study provides a comprehensive analysis of the effects of GSH under both physiological and oxidative stress conditions. Our study provides essential insights to direct the utilisation of GSH as a supplement in the management of conditions associated with oxidative stress. |
| first_indexed | 2024-04-25T00:23:29Z |
| format | Article |
| id | doaj.art-8ae046d0c57647408ef7a11c41df0117 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-25T00:23:29Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8ae046d0c57647408ef7a11c41df01172024-03-12T16:51:02ZengMDPI AGMolecules1420-30492024-02-01295109010.3390/molecules29051090Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 CellsYoshiaki Uchida0Farhana Ferdousi1Shinya Takahashi2Hiroko Isoda3Research and Development Division, Mitsubishi Corporation Life Sciences Ltd., 1-1-3 Yurakucho, Tokyo 100-0006, JapanInstitute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, JapanInstitute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, JapanInstitute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, JapanGlutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events regulated by GSH under physiological and oxidative stress conditions has also not been reported. In this study, DNA microarray analysis was performed with four experiment arms including Control, GSH, hydrogen peroxide (HP), and GSH + HP treatment groups. The GSH-treated group exhibited a significant upregulation of genes clustered in cell proliferation, growth, and differentiation, particularly those related to MAPK, when compared with the Control group. Additionally, liver functions such as alcohol and cholesterol metabolic processes were significantly upregulated. On the other hand, in the HP-induced oxidative stress condition, GSH (GSH + HP group) demonstrated a significant activation of cell proliferation, cell cycle, and various signalling pathways (including TGFβ, MAPK, PI3K/AKT, and HIF-1) in comparison to the HP group. Furthermore, several disease-related pathways, such as chemical carcinogenesis–reactive oxygen species and fibrosis, were significantly downregulated in the GSH + HP group compared to the HP group. Collectively, our study provides a comprehensive analysis of the effects of GSH under both physiological and oxidative stress conditions. Our study provides essential insights to direct the utilisation of GSH as a supplement in the management of conditions associated with oxidative stress.https://www.mdpi.com/1420-3049/29/5/1090glutathioneantioxidative stressreactive oxygen speciesDNA microarrayHepG2 cell |
| spellingShingle | Yoshiaki Uchida Farhana Ferdousi Shinya Takahashi Hiroko Isoda Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells Molecules glutathione antioxidative stress reactive oxygen species DNA microarray HepG2 cell |
| title | Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells |
| title_full | Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells |
| title_fullStr | Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells |
| title_full_unstemmed | Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells |
| title_short | Comprehensive Transcriptome Profiling of Antioxidant Activities by Glutathione in Human HepG2 Cells |
| title_sort | comprehensive transcriptome profiling of antioxidant activities by glutathione in human hepg2 cells |
| topic | glutathione antioxidative stress reactive oxygen species DNA microarray HepG2 cell |
| url | https://www.mdpi.com/1420-3049/29/5/1090 |
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