Toxicogenomic Analysis of Mainstream Tobacco Smoke-Exposed Mice Reveals Repression of Plasminogen Activator Inhibitor-1 Gene in Heart
| Autor: | Sabina Halappanavar, Andrew Williams, Martin R. Stämpfli, Carole L. Yauk, Lynn Berndt-Weis, George R. Douglas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
Health Toxicology and Mutagenesis Blotting Western Down-Regulation Enzyme-Linked Immunosorbent Assay Mice Transgenic 030204 cardiovascular system & hematology Biology Toxicology Toxicogenetics Tobacco smoke Article Gene Expression Regulation Enzymologic Andrology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Microsomes Gene expression Plasminogen Activator Inhibitor 1 Cytochrome P-450 CYP1A1 Animals 030304 developmental biology Oligonucleotide Array Sequence Analysis Regulation of gene expression 0303 health sciences Gene Expression Profiling Heart Molecular biology 3. Good health Cardiovascular physiology Up-Regulation Blot Gene expression profiling Mice Inbred C57BL chemistry Cardiovascular Diseases Plasminogen activator inhibitor-1 Mice Inbred CBA Tobacco Smoke Pollution Plasminogen activator |
| Zdroj: | Inhalation Toxicology |
| ISSN: | 1091-7691 0895-8378 |
| Popis: | Tobacco smoking is associated with cardiovascular pathology. However, the molecular mechanisms of tobacco smoke exposure that lead to initiation or exacerbation of cardiovascular disease are unclear. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the heart were investigated. Male C57B1/CBA mice were exposed to MTS from 2 cigarettes daily, 5 days/wk for 6 or 12 wk. Mice were sacrificed immediately, or 6 wk following the last cigarette. High-density DNA microarrays were used to characterize global gene expression changes in whole heart. Fifteen genes were significantly differentially expressed following exposure to MTS. Among these genes, cytochrome P-450 1A1 (Cyp1A1) was upregulated by 12-fold, and Serpine-1 (plasminogen activator inhibitor-1, PAI-1) was downregulated by 1.7-fold. Concomitant increase in Cyp1A1 protein levels and decrease in total and active PAI-1 protein was observed in tissue extracts by Western blot assay and enzyme-linked immunosorbent assay (ELISA), respectively. Observed changes were transient and were partially reversed during break periods. Thus, gene expression profiling of heart tissue revealed a novel cardiovascular mechanism operating in response to MTS. Our results suggest a potential role for PAI-1 in MTS-induced cardiovascular pathology. |
| Databáze: | OpenAIRE |
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