Inhalation of ammonia promotes apoptosis and induces autophagy in hepatocytes via Bax/BCl-2 and m-TOR/ATG5/LC-3bII axes
Copyright © 2023 Elsevier B.V. All rights reserved..
Ammonia (NH3) is an irritating gas and atmospheric pollutant that endangers the health of humans and animals by stimulating respiratory tract's mucosa and causing liver damage. However, physiological role of ammonia gas in hepatotoxicity remains unclear. To investigate the hepatotoxic effects of inhaled ammonia gas, experiments were conducted using mouse model exposed to 100 ppm of ammonia gas for 21 days. The exposed mice exhibited signs of depression, emaciation, and reduced growth. This study revealed that inhalation of ammonia led to significant decrease in water (P < 0.0001) and food intake (P < 0.05), resulting in slower growth. Histopathological analysis showed that ammonia stress alters the microstructure of the liver by enlarging the gap between hepatic lobule and fibrosis. Moreover, ammonia-induced stress significantly reduces the expression of the anti-apoptotic protein BCl-2 (P < 0.001), while elevates the mRNA expression of the pro-apoptotic gene Bax (P < 0.001). Furthermore, ammonia inhalation significantly increases the protein expression of LC-3bII (P < 0.05) and the mRNA expression of autophagy-related gene 5 (ATG5) (P < 0.05) and p62 (P < 0.05) while remarkably decreases the mRNA expression of mammalian target of rapamycin (m-TOR) (P < 0.05). In conclusion, this study demonstrates that inhalation of ammonia gas causes liver damage and suggests autophagy happening via m-TOR/p62/LC-3bII and pro-apoptosis effect mediated by Bax/BCl-2 in the liver damage caused by ammonia inhalation. Our study provides a new perspective on ammonia-induced hepatotoxicity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:912 |
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| Enthalten in: |
The Science of the total environment - 912(2024) vom: 20. Jan., Seite 169036 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Bohan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.01.2024 Date Revised 18.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.scitotenv.2023.169036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365525294 |
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| 245 | 1 | 0 | |a Inhalation of ammonia promotes apoptosis and induces autophagy in hepatocytes via Bax/BCl-2 and m-TOR/ATG5/LC-3bII axes |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Ammonia (NH3) is an irritating gas and atmospheric pollutant that endangers the health of humans and animals by stimulating respiratory tract's mucosa and causing liver damage. However, physiological role of ammonia gas in hepatotoxicity remains unclear. To investigate the hepatotoxic effects of inhaled ammonia gas, experiments were conducted using mouse model exposed to 100 ppm of ammonia gas for 21 days. The exposed mice exhibited signs of depression, emaciation, and reduced growth. This study revealed that inhalation of ammonia led to significant decrease in water (P < 0.0001) and food intake (P < 0.05), resulting in slower growth. Histopathological analysis showed that ammonia stress alters the microstructure of the liver by enlarging the gap between hepatic lobule and fibrosis. Moreover, ammonia-induced stress significantly reduces the expression of the anti-apoptotic protein BCl-2 (P < 0.001), while elevates the mRNA expression of the pro-apoptotic gene Bax (P < 0.001). Furthermore, ammonia inhalation significantly increases the protein expression of LC-3bII (P < 0.05) and the mRNA expression of autophagy-related gene 5 (ATG5) (P < 0.05) and p62 (P < 0.05) while remarkably decreases the mRNA expression of mammalian target of rapamycin (m-TOR) (P < 0.05). In conclusion, this study demonstrates that inhalation of ammonia gas causes liver damage and suggests autophagy happening via m-TOR/p62/LC-3bII and pro-apoptosis effect mediated by Bax/BCl-2 in the liver damage caused by ammonia inhalation. Our study provides a new perspective on ammonia-induced hepatotoxicity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ATG5/LC-3bII | |
| 650 | 4 | |a Ammonia | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Autophagy | |
| 650 | 4 | |a Bax/BCl-2 | |
| 650 | 4 | |a Hepatotoxicity | |
| 650 | 7 | |a bcl-2-Associated X Protein |2 NLM | |
| 650 | 7 | |a Ammonia |2 NLM | |
| 650 | 7 | |a 7664-41-7 |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a ATG5 protein, human |2 NLM | |
| 650 | 7 | |a Autophagy-Related Protein 5 |2 NLM | |
| 700 | 1 | |a Liu, Xiaoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Shouyan |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Junhong |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Chamba, Yangzom |e verfasserin |4 aut | |
| 700 | 1 | |a Mehmood, Khalid |e verfasserin |4 aut | |
| 700 | 1 | |a Fouad, Dalia |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hui |e verfasserin |4 aut | |
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