title: Proteomic characterization of early changes induced by triiodothyronine in rat liver.
abstract: High doses of T3 are mitogenic in liver, causing hyperplasia that has numerous differences from the compensatory regeneration induced by partial hepatectomy (PH). T3 binds to the thyroid hormone receptor (TR), which directly regulates transcription, while PH acts indirectly through signal transduction pathways. We therefore carried out a proteomic analysis to compare early effects of the two treatments. Transcriptome analysis by DNA microarray also confirmed the observed proteomic changes, demonstrating that they were caused by transcriptional regulation. Among the differentially expressed proteins, many are directly or indirectly involved in energy metabolism and response to oxidative stress. Several enzymes of lipid metabolism (e.g., Acaa2, Acads, Hadh, and Echs1) were differentially regulated by T3. In addition, altered expression levels of several mitochondrial proteins (e.g., Hspa9, Atp5b, Cps1, Glud1, Aldh2, Ak2, Acads) demonstrated the known increase of mitochondrial biogenesis mediated by T3. The present results provide insights in changes in metabolic balance occurring following T3-stimulation and define a basis for dissecting the molecular pathways of hepatocyte hyperplasia.
authors.affiliation: Department of Life Science, Second University of Naples, Via Vivaldi 43, I-81100 Caserta, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Severino
authors.forename: Joseph
authors.initials: J
authors.lastname: Locker
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Ledda-Columbano
authors.forename: Amedeo
authors.initials: A
authors.lastname: Columbano
authors.forename: Augusto
authors.initials: A
authors.lastname: Parente
authors.forename: Angela
authors.initials: A
authors.lastname: Chambery
mesh_terms: D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006498:Hepatectomy; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine