Abstract
In the current work, we studied how variations in extracellular zinc concentrations modulate different steps involved in nuclear factor κB (NF-κB) activation in human neuroblastoma IMR-32 cells. Cells were incubated in media containing varying concentrations of zinc (1.5, 5, 15, and 50 μM). Within 3 h, the intracellular zinc content was lower in cells exposed to 1.5 and 5 μM, compared with the other groups. Low intracellular zinc concentrations were associated with the activation of NF-κB, based on high levels of IκBα phosphorylation, low IκBα concentrations, and high NF-κB binding activity in total cell fractions. However, the active dimer accumulated in the cytosol, as shown by a low ratio of nuclear/cytosolic NF-κB binding activity. This altered nuclear translocation was accompanied by a decreased transactivation of an endogenous NF-κB-driven gene (ikba) and of a reporter gene (pNF-κB-luc). In cells with low intracellular zinc concentrations, a low rate of in vitro tubulin polymerization was measured compared with the other groups. We conclude that low intracellular zinc concentrations induce tubulin depolymerization, which may be one signal for NF-κB activation. However, NF-κB nuclear translocation is impaired, which inhibits the transactivation of NF-κB-driven genes. This could affect cell survival, and be an important factor in certain zinc deficiency-associated pathologies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 34610-34617 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 277 |
| Issue number | 37 |
| DOIs | |
| State | Published - Sep 13 2002 |
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ASJC Scopus subject areas
- Biochemistry
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Low intracellular zinc impairs the translocation of activated NF-κB to the nuclei in human neuroblastoma IMR-32 cells. / Mackenzie, Gerardo; Paola Zago, M.; Keen, Carl L; Oteiza, Patricia I.
In: Journal of Biological Chemistry, Vol. 277, No. 37, 13.09.2002, p. 34610-34617.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Low intracellular zinc impairs the translocation of activated NF-κB to the nuclei in human neuroblastoma IMR-32 cells
AU - Mackenzie, Gerardo
AU - Paola Zago, M.
AU - Keen, Carl L
AU - Oteiza, Patricia I.
PY - 2002/9/13
Y1 - 2002/9/13
N2 - In the current work, we studied how variations in extracellular zinc concentrations modulate different steps involved in nuclear factor κB (NF-κB) activation in human neuroblastoma IMR-32 cells. Cells were incubated in media containing varying concentrations of zinc (1.5, 5, 15, and 50 μM). Within 3 h, the intracellular zinc content was lower in cells exposed to 1.5 and 5 μM, compared with the other groups. Low intracellular zinc concentrations were associated with the activation of NF-κB, based on high levels of IκBα phosphorylation, low IκBα concentrations, and high NF-κB binding activity in total cell fractions. However, the active dimer accumulated in the cytosol, as shown by a low ratio of nuclear/cytosolic NF-κB binding activity. This altered nuclear translocation was accompanied by a decreased transactivation of an endogenous NF-κB-driven gene (ikba) and of a reporter gene (pNF-κB-luc). In cells with low intracellular zinc concentrations, a low rate of in vitro tubulin polymerization was measured compared with the other groups. We conclude that low intracellular zinc concentrations induce tubulin depolymerization, which may be one signal for NF-κB activation. However, NF-κB nuclear translocation is impaired, which inhibits the transactivation of NF-κB-driven genes. This could affect cell survival, and be an important factor in certain zinc deficiency-associated pathologies.
AB - In the current work, we studied how variations in extracellular zinc concentrations modulate different steps involved in nuclear factor κB (NF-κB) activation in human neuroblastoma IMR-32 cells. Cells were incubated in media containing varying concentrations of zinc (1.5, 5, 15, and 50 μM). Within 3 h, the intracellular zinc content was lower in cells exposed to 1.5 and 5 μM, compared with the other groups. Low intracellular zinc concentrations were associated with the activation of NF-κB, based on high levels of IκBα phosphorylation, low IκBα concentrations, and high NF-κB binding activity in total cell fractions. However, the active dimer accumulated in the cytosol, as shown by a low ratio of nuclear/cytosolic NF-κB binding activity. This altered nuclear translocation was accompanied by a decreased transactivation of an endogenous NF-κB-driven gene (ikba) and of a reporter gene (pNF-κB-luc). In cells with low intracellular zinc concentrations, a low rate of in vitro tubulin polymerization was measured compared with the other groups. We conclude that low intracellular zinc concentrations induce tubulin depolymerization, which may be one signal for NF-κB activation. However, NF-κB nuclear translocation is impaired, which inhibits the transactivation of NF-κB-driven genes. This could affect cell survival, and be an important factor in certain zinc deficiency-associated pathologies.
UR - http://www.scopus.com/inward/record.url?scp=0037072944&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037072944&partnerID=8YFLogxK
U2 - 10.1074/jbc.M203616200
DO - 10.1074/jbc.M203616200
M3 - Article
C2 - 12089148
AN - SCOPUS:0037072944
VL - 277
SP - 34610
EP - 34617
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 37
ER -