New insights about the posttranscriptional mechanisms triggered by iodide excess on sodium/iodide symporter (NIS) expression in PCCl3 cells

Mol Cell Endocrinol. 2012 Feb 26;349(2):154-61. doi: 10.1016/j.mce.2011.09.036. Epub 2011 Oct 1.

Abstract

Iodide excess acutely downregulates NIS mRNA expression, as already demonstrated. PCCl3 cells treated or not with NaI, NaI+NaClO(4) or NaI+Methimazole, for 30 min to 24 h, were used to further explore how iodide reduces NIS gene expression. NIS mRNA expression was evaluated by Real-Time PCR; its poly(A) tail length, by RACE-PAT; its translation rate, by polysome profile; total NIS content, by Western blotting. NIS mRNA decay rate was evaluated in actinomycin-D-treated cells, incubated with or without NaI for 0-6 h. Iodide treatment caused a reduction in NIS mRNA expression, half-life, poly(A) tail length, recruitment to ribosomes, as well as NIS protein expression. Perchlorate, but not methimazole, prevented these effects. Therefore, reduced poly(A) tail length of NIS mRNA seems to be related to its decreased half-life, in addition to its translation impairment. These data provide new insights about the molecular mechanisms involved in the rapid and posttranscriptional inhibitory effect of iodide on NIS expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithyroid Agents / pharmacology
  • Blotting, Western
  • Cell Line
  • Gene Expression / drug effects*
  • Half-Life
  • Methimazole / pharmacology
  • Perchlorates / pharmacology
  • Polyribosomes / chemistry
  • Polyribosomes / drug effects
  • Polyribosomes / genetics
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Sodium Compounds / pharmacology
  • Sodium Iodide / pharmacology*
  • Symporters / antagonists & inhibitors
  • Symporters / genetics
  • Symporters / metabolism*
  • Thyroid Gland / cytology
  • Thyroid Gland / drug effects*
  • Thyroid Gland / physiology

Substances

  • Antithyroid Agents
  • Perchlorates
  • RNA, Messenger
  • Sodium Compounds
  • Symporters
  • sodium-iodide symporter
  • Methimazole
  • sodium perchlorate
  • Sodium Iodide