| Abstract | 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. |
| Authors | A S Prasad, B Bao, F W Beck, F H Sarkar
(Affiliation: Department of Medicine, Division of Hematology-Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.)
|
| Journal | The Journal of laboratory and clinical medicine
(J Lab Clin Med)
Vol. 138
Issue 4
Pg. 250-6
(Oct 2001)
ISSN: 0022-2143 United States |
| PMID | 11574819
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- I-kappa B Proteins
- NF-kappa B
- Recombinant Proteins
- Ubiquitins
- Zinc
- DNA
- Luciferases
|
| Topics |
- Cell Line
- Cell Nucleus
(metabolism)
- Cytosol
(metabolism)
- DNA
(metabolism)
- Gene Expression
- Genes, Reporter
- Humans
- I-kappa B Proteins
(metabolism)
- Luciferases
(genetics, metabolism)
- Microscopy, Confocal
- NF-kappa B
(genetics, metabolism)
- Phosphorylation
- Recombinant Proteins
(metabolism)
- T-Lymphocytes
- Transfection
- Ubiquitins
(metabolism)
- Zinc
(deficiency, pharmacology, physiology)
|
