Heavy metal and growth hormone pathways in metallothionein regulation in fish RTH-149 cell line

Description

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 Zn2+/GH and Cd2+/GH, a negative interference for Hg2+/GH. With regards to MT-A, no interference was observed for Zn2+/GH and Hg2+/GH, while a negative interference occurred with Cu2+/GH and a positive interference with Cd2+/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 Zn2+/ GH and Cd2+/GH exerted a slight positive interference on ERK activation. On the other hand, a synergic rise in [Ca2+]i occurred for all combinations except for Cu2+/GH. Our data suggest that the cross-talk between heavy metals and GH resulting in MT transcription modulation does not strictly depend on Ca2+ signalling; (ii)ERK activation may represent the point of cross-talk between Zn2+ or Cd2+ and GH, converging on MT-B transcription, probably through a differential recruitment of transcription factors.

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