title: Efects of growth hormone and cadmium on the transcription regulation of two metallothionein isoforms.
abstract: The effect of growth hormone (GH) and cadmium (Cd) on metallothionein (MT) expression was investigated in hepatoma cells. In fish the constitutive isoform MT-B and the metal-responsive MT-A are expressed. Real-time RT-PCR revealed that: Cd up-regulates mostly MT-A, GH slightly induces MT-B and the GH/Cd combination induces synergistically both MTs. Perturbations in Ca2+ levels suppressed or reduced the Cd-induction of MTs and abolished the GH/Cd synergy. Similar results were obtained by inhibition of tyrosine kinases. Also the signaling molecules recruited by the GH receptor responded differently to GH and Cd, with ERKs showing a synergistic activation upon GH/Cd. The following conclusions can be drawn: (1) cytosolic Ca2+ is mainly involved in MT-A regulation; (2) both Ca2+ and tyrosine phosphorylation are essential for Cd-induction and GH/Cd synergy on MTs. The synergy could depend on interactions in different signaling pathways, leading to a differential recruitment of MTF-1 and AP-1 transcription factors.
authors.affiliation: Department of Biophysical Sciences and Technologies M. & O (DISTBIMO), University of Genoa, Largo Rosanna Benzi 10, 16132 Genova, Italy. Laura.Vergani@unige.it
authors.forename: Laura
authors.initials: L
authors.lastname: Vergani
authors.forename: Cristina
authors.initials: C
authors.lastname: Lanza
authors.forename: Cristina
authors.initials: C
authors.lastname: Borghi
authors.forename: Linda
authors.initials: L
authors.lastname: Scarabelli
authors.forename: Isabella
authors.initials: I
authors.lastname: Panfoli
authors.forename: Bruno
authors.initials: B
authors.lastname: Burlando
authors.forename: Francesco
authors.initials: F
authors.lastname: Dondero
authors.forename: Aldo
authors.initials: A
authors.lastname: Viarengo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gallo
mesh_terms: D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D000097809:Transcription Factor MTF-1
chemical_list: D002104:Cadmium; D002118:Calcium; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D008668:Metallothionein; D020928:Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014443:Tyrosine; D000097809:Transcription Factor MTF-1