Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 263, Issue 1-2, Pages 29-37Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2006.08.010
Keywords
metallothionein regulation; calcium signaling; tyrosine kinase signaling; MAP kinases; real-time RT-PCR; RTH 149 trout hepatoma cells
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The effect of growth hormone (GH) and cadmium (Cd) on metallothionein (NIT) 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 NIT-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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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