Eukaryotic initiation factor 2alpha kinase is a nitric oxide-responsive mercury sensor enzyme: potent inhibition of catalysis by the mercury cation and reversal by nitric oxide.
The activity of one of the eukaryotic initiation factor 2alpha kinases, heme-regulated inhibitor (HRI), is modulated by heme binding. Here, we demonstrate for the first time that Hg2+ strongly inhibits the function of HRI (IC50=0.6 microM), and nitric oxide fully reverses this inhibition. Other divalent metal cations, such as Fe2+, Cu2+, Cd2+, Zn2+ and Pb2+, also significantly inhibit kinase activity with IC50 values of 1.9-8.5 microM. Notably, inhibition by cations other than Hg2+ is not reversed by nitric oxide. Our present data support dual roles of Hg2+ and nitric oxide in the regulation of protein synthesis during cell emergency states.
Martinkova
Marketa
M
Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Sendai 980-8577, Japan.
Igarashi
Jotaro
J
Shimizu
Toru
T
D000818:Animals; D002384:Catalysis / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008628:Mercury / Q000494:pharmacology*; D019216:Metals, Heavy / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
D002413:Cations, Divalent; D019216:Metals, Heavy; D009569:Nitric Oxide; D019892:eIF-2 Kinase; D008628:Mercury