Alcohol-induced liver disease: when fat and oxidative stress meet
Reactive oxygen species (ROS) act as signaling intermediates regulting multiple cellular processes. The fate and disposal of the signaling species are determined by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial pool of GSH (mGSH) arises from the transport of cytosol...
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| Format: | Article |
| Language: | English |
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Elsevier
2003-04-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119321441 |
| _version_ | 1829478898352521216 |
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| author | José C. Fernández-Checa, MD, PhD |
| author_facet | José C. Fernández-Checa, MD, PhD |
| author_sort | José C. Fernández-Checa, MD, PhD |
| collection | DOAJ |
| description | Reactive oxygen species (ROS) act as signaling intermediates regulting multiple cellular processes. The fate and disposal of the signaling species are determined by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial pool of GSH (mGSH) arises from the transport of cytosol GSH by a specific mitochondrial carrier and is responsible for the maintenance of a healthy competent organelle. The depletion of mGSH upon impairment of the mitochondrial transport activity leaves mitochondria unprotected from damaging effects of ROS overgeneration within the mitochondrial electron transport chain. Tumor necrosis factor-α (TNF-α) has emerged as a key player in the progression of the alcohol-induced liver disease (ALD), and is known to target mitochondria. Key components of TNF signaling include sphingolipids, particularly ceramide generated from acidic sphingomyelinase activation serving as a source for gangliosides. In experimental models alcohol consumption enhances cholesterol levels and subsequent deposition into mitochondria resulting in selective decrease in the mGSH stores which is sufficient by itself to sensitize hepatocytes to TNF-α-mediated cell death. Thus, the combination of TNF-α overproduction, enhanced glycosphingolipid generation and selective mGSH depletion by alcohol intake cooperate making the liver sensitive to alcohol. |
| first_indexed | 2024-12-14T17:25:10Z |
| format | Article |
| id | doaj.art-de60794159f549838776811d5940ec14 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-14T17:25:10Z |
| publishDate | 2003-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-de60794159f549838776811d5940ec142022-12-21T22:53:14ZengElsevierAnnals of Hepatology1665-26812003-04-01226975Alcohol-induced liver disease: when fat and oxidative stress meetJosé C. Fernández-Checa, MD, PhD0Liver Unit, Instituto Malalties Digestives, Hospital Clinic i Provincial, Instituto Investigaciones Biomédicas August Pi i Sunyer, and Department of Experimental Pathology, Instituto Investigaciones Biomédicas Barcelona, Consejo Superior Investigaciones Científicas, Barcelona 08036, Spain; Address for correspondence:Reactive oxygen species (ROS) act as signaling intermediates regulting multiple cellular processes. The fate and disposal of the signaling species are determined by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial pool of GSH (mGSH) arises from the transport of cytosol GSH by a specific mitochondrial carrier and is responsible for the maintenance of a healthy competent organelle. The depletion of mGSH upon impairment of the mitochondrial transport activity leaves mitochondria unprotected from damaging effects of ROS overgeneration within the mitochondrial electron transport chain. Tumor necrosis factor-α (TNF-α) has emerged as a key player in the progression of the alcohol-induced liver disease (ALD), and is known to target mitochondria. Key components of TNF signaling include sphingolipids, particularly ceramide generated from acidic sphingomyelinase activation serving as a source for gangliosides. In experimental models alcohol consumption enhances cholesterol levels and subsequent deposition into mitochondria resulting in selective decrease in the mGSH stores which is sufficient by itself to sensitize hepatocytes to TNF-α-mediated cell death. Thus, the combination of TNF-α overproduction, enhanced glycosphingolipid generation and selective mGSH depletion by alcohol intake cooperate making the liver sensitive to alcohol.http://www.sciencedirect.com/science/article/pii/S1665268119321441AlcoholLiver damageMitochondriaReactive oxigen species |
| spellingShingle | José C. Fernández-Checa, MD, PhD Alcohol-induced liver disease: when fat and oxidative stress meet Annals of Hepatology Alcohol Liver damage Mitochondria Reactive oxigen species |
| title | Alcohol-induced liver disease: when fat and oxidative stress meet |
| title_full | Alcohol-induced liver disease: when fat and oxidative stress meet |
| title_fullStr | Alcohol-induced liver disease: when fat and oxidative stress meet |
| title_full_unstemmed | Alcohol-induced liver disease: when fat and oxidative stress meet |
| title_short | Alcohol-induced liver disease: when fat and oxidative stress meet |
| title_sort | alcohol induced liver disease when fat and oxidative stress meet |
| topic | Alcohol Liver damage Mitochondria Reactive oxigen species |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119321441 |
| work_keys_str_mv | AT josecfernandezchecamdphd alcoholinducedliverdiseasewhenfatandoxidativestressmeet |