Please use this identifier to cite or link to this item:
http://digitalrepository.fccollege.edu.pk/handle/123456789/1244
Title: | Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death |
Authors: | Dunning, Sandra Rehman, Atta Ur Tiebosch, Marjolein H. Hannivoort, , Rebekka A. Haijer, Floris W. Woudenberg, Jannes Heuvel, Fiona A.J. van den Homan, Manon Buist- Faber, Klaas Nico Moshage, Han |
Keywords: | Cell death Oxidative stress Glutathione peroxidase Catalase Superoxide dismutase |
Issue Date: | Dec-2013 |
Publisher: | ELSEVIER |
Citation: | Sandra Dunning, Atta ur Rehman, Marjolein H. Tiebosch, Rebekka A. Hannivoort, Floris W. Haijer, Jannes Woudenberg, Fiona A.J. van den Heuvel, Manon Buist-Homan, Klaas Nico Faber, Han Moshage, Glutathione and antioxidant enzymes serve complementary roles in protecting activated hepatic stellate cells against hydrogen peroxide-induced cell death, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1832, Issue 12, 2013, Pages 2027-2034, ISSN 0925-4439, https://doi.org/10.1016/j.bbadis.2013.07.008. |
Series/Report no.: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1832, Issue 12, 2013, Pages 2027-2034,; |
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-peroxidase (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. |
Description: | https://www.sciencedirect.com/science/article/pii/S0925443913002482 |
URI: | http://localhost:8080/xmlui/handle/123456789/1244 |
Appears in Collections: | Pharmacy Department |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
20130701 Dunning-UrRehman-Tiebosch-BBA3013.pdf | 782.09 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.