Cargando…
Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver
Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 4...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321199/ https://www.ncbi.nlm.nih.gov/pubmed/30567393 http://dx.doi.org/10.3390/ijms19124114 |
_version_ | 1783385385142845440 |
---|---|
author | Kim, Sou Hyun Kwon, Do-young Kwak, Jae-Hwan Lee, Seunghyun Lee, Yun-Hee Yun, Jieun Son, Tae Gen Jung, Young-Suk |
author_facet | Kim, Sou Hyun Kwon, Do-young Kwak, Jae-Hwan Lee, Seunghyun Lee, Yun-Hee Yun, Jieun Son, Tae Gen Jung, Young-Suk |
author_sort | Kim, Sou Hyun |
collection | PubMed |
description | Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 48 h to induce ER stress in the liver and examined the metabolic pathway that synthesizes the endogenous antioxidant, glutathione (GSH). Tunicamycin (TM) treatment significantly increased mRNA levels of CHOP and GRP78, and induced lipid accumulation in the liver. Lipid peroxidation in the liver tissue also increased from TM treatment (CON vs. TM; 3.0 ± 1.8 vs. 11.1 ± 0.8 nmol MDA/g liver, p < 0.001), which reflects an imbalance between the generation of reactive substances and antioxidant capacity. To examine the involvement of GSH synthetic pathway, we determined the metabolomic changes of sulfur amino acids in the liver. TM significantly decreased hepatic S-adenosylmethionine concentration in the methionine cycle. The levels of cysteine in the liver were increased, while taurine concentration was maintained and GSH levels profoundly decreased (CON vs. TM; 8.7 ± 1.5 vs. 5.4 ± 0.9 µmol GSH/g liver, p < 0.001). These results suggest that abnormal cysteine metabolism by TM treatment resulted in a decrease in GSH, followed by an increase in oxidative stress in the liver. In HepG2 cells, decreased GSH levels were examined by TM treatment in a dose dependent manner. Furthermore, pretreatment with TM in HepG2 cells potentiated oxidative cell death, by exacerbating the effects of tert-butyl hydroperoxide. In conclusion, TM-induced ER stress was accompanied by oxidative stress by reducing the GSH synthesis, which made the liver more susceptible to oxidative stress. |
format | Online Article Text |
id | pubmed-6321199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63211992019-01-07 Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver Kim, Sou Hyun Kwon, Do-young Kwak, Jae-Hwan Lee, Seunghyun Lee, Yun-Hee Yun, Jieun Son, Tae Gen Jung, Young-Suk Int J Mol Sci Article Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 48 h to induce ER stress in the liver and examined the metabolic pathway that synthesizes the endogenous antioxidant, glutathione (GSH). Tunicamycin (TM) treatment significantly increased mRNA levels of CHOP and GRP78, and induced lipid accumulation in the liver. Lipid peroxidation in the liver tissue also increased from TM treatment (CON vs. TM; 3.0 ± 1.8 vs. 11.1 ± 0.8 nmol MDA/g liver, p < 0.001), which reflects an imbalance between the generation of reactive substances and antioxidant capacity. To examine the involvement of GSH synthetic pathway, we determined the metabolomic changes of sulfur amino acids in the liver. TM significantly decreased hepatic S-adenosylmethionine concentration in the methionine cycle. The levels of cysteine in the liver were increased, while taurine concentration was maintained and GSH levels profoundly decreased (CON vs. TM; 8.7 ± 1.5 vs. 5.4 ± 0.9 µmol GSH/g liver, p < 0.001). These results suggest that abnormal cysteine metabolism by TM treatment resulted in a decrease in GSH, followed by an increase in oxidative stress in the liver. In HepG2 cells, decreased GSH levels were examined by TM treatment in a dose dependent manner. Furthermore, pretreatment with TM in HepG2 cells potentiated oxidative cell death, by exacerbating the effects of tert-butyl hydroperoxide. In conclusion, TM-induced ER stress was accompanied by oxidative stress by reducing the GSH synthesis, which made the liver more susceptible to oxidative stress. MDPI 2018-12-18 /pmc/articles/PMC6321199/ /pubmed/30567393 http://dx.doi.org/10.3390/ijms19124114 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Sou Hyun Kwon, Do-young Kwak, Jae-Hwan Lee, Seunghyun Lee, Yun-Hee Yun, Jieun Son, Tae Gen Jung, Young-Suk Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title | Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title_full | Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title_fullStr | Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title_full_unstemmed | Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title_short | Tunicamycin-Induced ER Stress is Accompanied with Oxidative Stress via Abrogation of Sulfur Amino Acids Metabolism in the Liver |
title_sort | tunicamycin-induced er stress is accompanied with oxidative stress via abrogation of sulfur amino acids metabolism in the liver |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321199/ https://www.ncbi.nlm.nih.gov/pubmed/30567393 http://dx.doi.org/10.3390/ijms19124114 |
work_keys_str_mv | AT kimsouhyun tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT kwondoyoung tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT kwakjaehwan tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT leeseunghyun tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT leeyunhee tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT yunjieun tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT sontaegen tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver AT jungyoungsuk tunicamycininducederstressisaccompaniedwithoxidativestressviaabrogationofsulfuraminoacidsmetabolismintheliver |