Differential regulation of zinc efflux transporters ZnT-1, ZnT-5 and ZnT-7 gene expression by zinc levels: a real-time RT-PCR study.
Intracellular zinc levels are strictly regulated by zinc channels and zinc-binding proteins to maintain cellular zinc-dependent functions. We demonstrated a correlation between extracellular zinc concentration and intracellular exchangeable zinc levels using the fluorescent zinc-specific probes zinquin and zinpyr-1. The effect of extracellular zinc status on the regulation of the two trans-Golgi network directed zinc transporters ZnT-5 and ZnT-7 was next studied by real-time RT-PCR in zinc supplemented or depleted HeLa cells. While sub-toxic extracellular zinc addition strongly induced the efflux transporter ZnT-1 gene expression, consistent with its activation by the transcription factor MTF-1, treated HeLa cells did not display any change in ZnT-5 and ZnT-7 mRNA levels compared to control cells. In contrast, zinc depletion induced by non-toxic doses of the zinc chelator TPEN (N,N,N',N' tetrakis-(2 pyridylmethyl) ethylene diamine) resulted in a up to eight-fold induction of transporters ZnT-5 and ZnT-7 mRNA levels, providing the first evidence of a transcriptional control of these two zinc efflux transporters by zinc deficiency in cultured cells.
Laboratoire des lésions des acides nucléiques, DRFMC/SCIB/LAN, CEA/Grenoble, 17 rue des Martyrs, 38000 Grenoble, France.
Séverine
S
Devergnas
Fabrice
F
Chimienti
Nadège
N
Naud
André
A
Pennequin
Yoann
Y
Coquerel
Jocelyne
J
Chantegrel
Alain
A
Favier
Michel
M
Seve
D027682:Cation Transport Proteins; D002470:Cell Survival / Q000187:drug effects; D005029:Ethylenediamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015032:Zinc / Q000494:pharmacology*
D027682:Cation Transport Proteins; D005029:Ethylenediamines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C457225:SLC30A5 protein, human; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine