Zinc activates NF-kappaB in HUT-78 cells.
Zinc is essential for human health, and its deficiency in human beings results in growth failure, immune disorders affecting Th1 functions, decreased interleukin-2 (IL-2) production, and cognitive impairment. Nearly 2000 transcription factors require zinc for their structural integrity; however, it is not known whether cellular zinc deficiency results in any change in activation of any of the transcription factors. Inasmuch as NF-kappaB binds to the promoter enhancer area of IL-2 and IL-2Ralpha genes, we investigated the effect of zinc deficiency on activation of NF-kappaB and its binding to DNA in HUT-78, a Th0 malignant human lymphoblastoid cell line. We show here for the first time that in zinc-deficient HUT-78 cells, phosphorylated IkappaB, and IKK, ubiquitinated IkappaB and binding of NF-kappaB to DNA were all significantly decreased. Zinc increased the translocation of NF-kappaB from cytosol to nucleus. We also demonstrate that the binding of recombinant NF-kappaB (p50)(2) to DNA in HUT-78 cells was zinc specific. We conclude that zinc plays an important role in the activation of NF-kappaB in HUT-78 cells.
Prasad
A S
AS
Department of Medicine, Division of Hematology-Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Bao
B
B
Beck
F W
FW
Sarkar
F H
FH
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes; D014162:Transfection; D014452:Ubiquitins / Q000378:metabolism; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*
D020672:I-kappa B Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D014452:Ubiquitins; D004247:DNA; D008156:Luciferases; D015032:Zinc