Heavy metal and growth hormone pathways in metallothionein regulation in fish RTH-149 cell line.
Interference between heavy metals and growth hormone (GH) on cell signaling has been previously demonstrated in fish cells. This study was aimed at assessing their effects on expression of the metallothionein isoforms MT-A and MT-B. The results indicate that all heavy metals induce MT-A more markedly than MT-B, but differences appeared when metals were combined with GH. For MT-B induction, a positive interference between metals and GH was observed for Zn(2+)/GH and Cd(2+)/GH, a negative interference for Hg(2+)/GH. With regards to MT-A, no interference was observed for Zn(2+)/GH and Hg(2+)/GH, while a negative interference occurred with Cu(2+)/GH and a positive interference with Cd(2+)/GH. The possible mechanisms underlying the differential regulation of metallothioneins include different signaling pathways. The results show that STAT5 and ERKs responded differently to different combinations, and Zn(2+)/GH and Cd(2+)/GH exerted a slight positive interference on ERK activation. On the other hand, a synergic rise in [Ca(2+)](i) occurred for all combinations except for Cu(2+)/GH. Our data suggest that the cross-talk between heavy metals and GH resulting in MT transcription modulation does not strictly depend on Ca(2+) signalling; (ii)ERK activation may represent the point of cross-talk between Zn(2+) or Cd(2+) and GH, converging on MT-B transcription, probably through a differential recruitment of transcription factors.
Vergani
Laura
L
Department of Biology, University of Genova, Genova, Italy. Laura.Vergani@unige.it
Lanza
Cristina
C
Scarabelli
Linda
L
Canesi
Laura
L
Gallo
Gabriella
G
D000818:Animals; D002104:Cadmium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D008668:Metallothionein / Q000096:biosynthesis / Q000378:metabolism*; D019216:Metals, Heavy / Q000378:metabolism* / Q000494:pharmacology; D017686:Oncorhynchus mykiss; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology
D019216:Metals, Heavy; D050799:STAT5 Transcription Factor; D002104:Cadmium; D013006:Growth Hormone; D008668:Metallothionein; D048049:Extracellular Signal-Regulated MAP Kinases; D015032:Zinc; D002118:Calcium