Profile of stress and toxicity gene expression in human hepatic cells treated with Efavirenz
| Autor: | Miguel Martí-Cabrera, L.J. Gómez-Sucerquia, Ana Blas-Garcia, Nadezda Apostolova, Juan V. Esplugues |
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| Rok vydání: | 2012 |
| Předmět: |
Cyclopropanes
Chemokine Efavirenz Anti-HIV Agents Pharmacology Mitochondrion medicine.disease_cause Cell Line chemistry.chemical_compound Stress Physiological Virology Gene expression medicine Humans CXCL10 biology Gene Expression Profiling Molecular biology Benzoxazines Mitochondria Oxidative Stress chemistry Alkynes Toxicity Hepatocytes biology.protein Hepatic stellate cell Oxidative stress |
| Zdroj: | Antiviral Research. 94:232-241 |
| ISSN: | 0166-3542 |
| Popis: | Hepatic toxicity and metabolic disorders are major adverse effects elicited during the pharmacological treatment of the human immunodeficiency virus (HIV) infection. Efavirenz (EFV), the most widely used non-nucleoside reverse transcriptase inhibitor (NNRTI), has been associated with these events, with recent studies implicating it in stress responses involving mitochondrial dysfunction and oxidative stress in human hepatic cells. To expand these findings, we analyzed the influence of EFV on the expression profile of selected stress and toxicity genes in these cells. Significant up-regulation was observed with Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), which indicated metabolic stress. Several genes directly related to oxidative stress and damage exhibited increased expression, including Methalothionein 2A (MT2A), Heat shock 70kDa protein 6 (HSPA6), Growth differentiation factor 15 (GDF15) and DNA-damage-inducible transcript 3 (DDIT3). In addition, Early growth response protein 1 (EGR1) was enhanced, whereas mRNA levels of the inflammatory genes Chemokine (C-X-C motif) ligand 10 (CXCL10) and Serpin peptidase inhibitor (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1) decreased and increased, respectively. This profile of gene expression supports previous data demonstrating altered mitochondrial function and presence of oxidative stress/damage in EFV-treated hepatic cells, and may be of relevance in the search for molecular targets with therapeutic potential to be employed in the prevention, diagnosis and treatment of the hepatic toxicity associated with HIV therapy. |
| Databáze: | OpenAIRE |
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