Publication

Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death

Dunning, S., Rehman, A. U., Tiebosch, M. H., Hannivoort, R. A., Haijer, F. W., Woudenberg, J., van den Heuvel, F. A. J., Buist-Homan, M., Faber, K. N. & Moshage, H., Dec-2013, In : Biochimica et biophysica acta-Molecular basis of disease. 1832, 12, p. 2027-2034 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Dunning, S., Rehman, A. U., Tiebosch, M. H., Hannivoort, R. A., Haijer, F. W., Woudenberg, J., ... Moshage, H. (2013). Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochimica et biophysica acta-Molecular basis of disease, 1832(12), 2027-2034. https://doi.org/10.1016/j.bbadis.2013.07.008

Author

Dunning, Sandra ; Rehman, Atta Ur ; Tiebosch, Marjolein H. ; Hannivoort, Rebekka A. ; Haijer, Floris W. ; Woudenberg, Jannes ; van den Heuvel, Fiona A. J. ; Buist-Homan, Manon ; Faber, Klaas Nico ; Moshage, Han. / Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. In: Biochimica et biophysica acta-Molecular basis of disease. 2013 ; Vol. 1832, No. 12. pp. 2027-2034.

Harvard

Dunning, S, Rehman, AU, Tiebosch, MH, Hannivoort, RA, Haijer, FW, Woudenberg, J, van den Heuvel, FAJ, Buist-Homan, M, Faber, KN & Moshage, H 2013, 'Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death', Biochimica et biophysica acta-Molecular basis of disease, vol. 1832, no. 12, pp. 2027-2034. https://doi.org/10.1016/j.bbadis.2013.07.008

Standard

Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. / Dunning, Sandra; Rehman, Atta Ur; Tiebosch, Marjolein H.; Hannivoort, Rebekka A.; Haijer, Floris W.; Woudenberg, Jannes; van den Heuvel, Fiona A. J.; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han.

In: Biochimica et biophysica acta-Molecular basis of disease, Vol. 1832, No. 12, 12.2013, p. 2027-2034.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Dunning S, Rehman AU, Tiebosch MH, Hannivoort RA, Haijer FW, Woudenberg J et al. Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death. Biochimica et biophysica acta-Molecular basis of disease. 2013 Dec;1832(12):2027-2034. https://doi.org/10.1016/j.bbadis.2013.07.008


BibTeX

@article{0d603ec90a174bd7998db3fffd7e18f2,
title = "Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death",
abstract = "Background: In chronic liver disease, hepatic stellate cells (HSCs) are activated, highly proliferative and produce excessive amounts of extracellular matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen species (ROS) produced during chronic liver injury have been implicated in this activation process. Therefore, activated hepatic stellate cells need to harbor highly effective anti-oxidants to protect against the toxic effects of ROS.Aim: To investigate the protective mechanisms of activated HSCs against ROS-induced toxicity.Methods: Culture-activated rat HSCs were exposed to hydrogen peroxide. Necrosis and apoptosis were determined by Sytox Green or acridine orange staining, respectively. The hydrogen peroxide detoxifying enzymes catalase and glutathione-pefoxidase (GPx) were inhibited using 3-amino-1,2,4-triazole and mercaptosuccinic acid, respectively. The anti-oxidant glutathione was depleted by L-buthionine-sulfoximine and repleted with the GSH-analogue GSH-monoethylester (GSH-MEE).Results: Upon activation, HSCs increase their cellular glutathione content and GPx expression, while MnSOD (both at mRNA and protein level) and catalase (at the protein level, but not at the mRNA level) decreased. Hydrogen peroxide did not induce cell death in activated HSCs. Glutathione depletion increased the sensitivity of HSCs to hydrogen peroxide, resulting in 35{\%} and 75{\%} necrotic cells at 0.2 and 1 mmol/L hydrogen peroxide, respectively. The sensitizing effect was abolished by GSH-MEE. Inhibition of catalase or GPx significantly increased hydrogen peroxide-induced apoptosis, which was not reversed by GSH-MEE.Conclusion: Activated HSCs have increased ROS-detoxifying capacity compared to quiescent HSCs. Glutathione levels increase during HSC activation and protect against ROS-induced necrosis, whereas hydrogen peroxide-detoxifying enzymes protect against apoptotic cell death. (C) 2013 Elsevier B.V. All rights reserved.",
keywords = "Oxidative stress, Glutathione peroxidase, Catalase, Superoxide dismutase, Cell death, GAMMA-GLUTAMYLCYSTEINE SYNTHETASE, MANGANESE SUPEROXIDE-DISMUTASE, OXIDATIVE STRESS, ANTIFIBROGENIC PROTEIN, DEFICIENT MICE, LIVER-INJURY, PROLIFERATION, MECHANISMS, EXPRESSION, MOUSE",
author = "Sandra Dunning and Rehman, {Atta Ur} and Tiebosch, {Marjolein H.} and Hannivoort, {Rebekka A.} and Haijer, {Floris W.} and Jannes Woudenberg and {van den Heuvel}, {Fiona A. J.} and Manon Buist-Homan and Faber, {Klaas Nico} and Han Moshage",
year = "2013",
month = "12",
doi = "10.1016/j.bbadis.2013.07.008",
language = "English",
volume = "1832",
pages = "2027--2034",
journal = "Biochimica et biophysica acta-Molecular basis of disease",
issn = "0925-4439",
publisher = "ELSEVIER SCIENCE BV",
number = "12",

}

RIS

TY - JOUR

T1 - Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death

AU - Dunning, Sandra

AU - Rehman, Atta Ur

AU - Tiebosch, Marjolein H.

AU - Hannivoort, Rebekka A.

AU - Haijer, Floris W.

AU - Woudenberg, Jannes

AU - van den Heuvel, Fiona A. J.

AU - Buist-Homan, Manon

AU - Faber, Klaas Nico

AU - Moshage, Han

PY - 2013/12

Y1 - 2013/12

N2 - Background: In chronic liver disease, hepatic stellate cells (HSCs) are activated, highly proliferative and produce excessive amounts of extracellular matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen species (ROS) produced during chronic liver injury have been implicated in this activation process. Therefore, activated hepatic stellate cells need to harbor highly effective anti-oxidants to protect against the toxic effects of ROS.Aim: To investigate the protective mechanisms of activated HSCs against ROS-induced toxicity.Methods: Culture-activated rat HSCs were exposed to hydrogen peroxide. Necrosis and apoptosis were determined by Sytox Green or acridine orange staining, respectively. The hydrogen peroxide detoxifying enzymes catalase and glutathione-pefoxidase (GPx) were inhibited using 3-amino-1,2,4-triazole and mercaptosuccinic acid, respectively. The anti-oxidant glutathione was depleted by L-buthionine-sulfoximine and repleted with the GSH-analogue GSH-monoethylester (GSH-MEE).Results: Upon activation, HSCs increase their cellular glutathione content and GPx expression, while MnSOD (both at mRNA and protein level) and catalase (at the protein level, but not at the mRNA level) decreased. Hydrogen peroxide did not induce cell death in activated HSCs. Glutathione depletion increased the sensitivity of HSCs to hydrogen peroxide, resulting in 35% and 75% necrotic cells at 0.2 and 1 mmol/L hydrogen peroxide, respectively. The sensitizing effect was abolished by GSH-MEE. Inhibition of catalase or GPx significantly increased hydrogen peroxide-induced apoptosis, which was not reversed by GSH-MEE.Conclusion: Activated HSCs have increased ROS-detoxifying capacity compared to quiescent HSCs. Glutathione levels increase during HSC activation and protect against ROS-induced necrosis, whereas hydrogen peroxide-detoxifying enzymes protect against apoptotic cell death. (C) 2013 Elsevier B.V. All rights reserved.

AB - Background: In chronic liver disease, hepatic stellate cells (HSCs) are activated, highly proliferative and produce excessive amounts of extracellular matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen species (ROS) produced during chronic liver injury have been implicated in this activation process. Therefore, activated hepatic stellate cells need to harbor highly effective anti-oxidants to protect against the toxic effects of ROS.Aim: To investigate the protective mechanisms of activated HSCs against ROS-induced toxicity.Methods: Culture-activated rat HSCs were exposed to hydrogen peroxide. Necrosis and apoptosis were determined by Sytox Green or acridine orange staining, respectively. The hydrogen peroxide detoxifying enzymes catalase and glutathione-pefoxidase (GPx) were inhibited using 3-amino-1,2,4-triazole and mercaptosuccinic acid, respectively. The anti-oxidant glutathione was depleted by L-buthionine-sulfoximine and repleted with the GSH-analogue GSH-monoethylester (GSH-MEE).Results: Upon activation, HSCs increase their cellular glutathione content and GPx expression, while MnSOD (both at mRNA and protein level) and catalase (at the protein level, but not at the mRNA level) decreased. Hydrogen peroxide did not induce cell death in activated HSCs. Glutathione depletion increased the sensitivity of HSCs to hydrogen peroxide, resulting in 35% and 75% necrotic cells at 0.2 and 1 mmol/L hydrogen peroxide, respectively. The sensitizing effect was abolished by GSH-MEE. Inhibition of catalase or GPx significantly increased hydrogen peroxide-induced apoptosis, which was not reversed by GSH-MEE.Conclusion: Activated HSCs have increased ROS-detoxifying capacity compared to quiescent HSCs. Glutathione levels increase during HSC activation and protect against ROS-induced necrosis, whereas hydrogen peroxide-detoxifying enzymes protect against apoptotic cell death. (C) 2013 Elsevier B.V. All rights reserved.

KW - Oxidative stress

KW - Glutathione peroxidase

KW - Catalase

KW - Superoxide dismutase

KW - Cell death

KW - GAMMA-GLUTAMYLCYSTEINE SYNTHETASE

KW - MANGANESE SUPEROXIDE-DISMUTASE

KW - OXIDATIVE STRESS

KW - ANTIFIBROGENIC PROTEIN

KW - DEFICIENT MICE

KW - LIVER-INJURY

KW - PROLIFERATION

KW - MECHANISMS

KW - EXPRESSION

KW - MOUSE

U2 - 10.1016/j.bbadis.2013.07.008

DO - 10.1016/j.bbadis.2013.07.008

M3 - Article

VL - 1832

SP - 2027

EP - 2034

JO - Biochimica et biophysica acta-Molecular basis of disease

JF - Biochimica et biophysica acta-Molecular basis of disease

SN - 0925-4439

IS - 12

ER -

ID: 5998243