Differential modulation of MAP kinases by Zinc deficiency in IMR-32 cells: Role of H2O2.

PAOLA ZAGO; GERARDO G. MACKENZIE; ANA M. ADAMO; CARL L. KEEN; PATRICIA OTEIZA

ANTIOXIDANTS & REDOX SIGNALING

Mary Ann Liebert, Inc.

Lugar: New Rochelle, NY; Año: 2005 vol. 7 p. 1773 - 1782

1523-0864

The influence of zinc deficiency on the modulation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK1/2), p38, and c-Jun N-terminal kinase (JNK) was studied. Using human IMR-32 cells as a model of neuronal cells, the role of oxidants on MAPKs and activator protein-1 (AP-1) activation in zinc deficiency was investigated, characterizing the participation of these events in the triggering of apoptosis. Relative to controls, cells incubated in media with low zinc concentrations showed increased cell oxidants and hydrogen peroxide (H2O2) release, increased JNK and p38 activation, high nuclear AP-1-DNA binding activity, and AP-1-dependent gene expression. Catalase addition to the media prevented the increase of cellular oxidants and inhibited JNK, p38, and AP-1 activation. Low levels of ERK1/2 phosphorylation were observed in the zinc-deficient cells in association with a reduction in cell proliferation. Catalase treatment did not prevent the above events nor the increased rate of apoptosis in the zinc-deficient cells. It is first demonstrated that a decrease in cellular zinc triggers H2O2-independent, as well as H2O2-dependent effects on MAPKs. Zinc deficiency-induced increases in cellular H2O2 can trigger the activation of JNK and p38, leading to AP-1 activation, events that are not involved in zinc deficiency-induced apoptosis. Antioxid. Redox Signal. 7, 1773–1782.2O2) release, increased JNK and p38 activation, high nuclear AP-1-DNA binding activity, and AP-1-dependent gene expression. Catalase addition to the media prevented the increase of cellular oxidants and inhibited JNK, p38, and AP-1 activation. Low levels of ERK1/2 phosphorylation were observed in the zinc-deficient cells in association with a reduction in cell proliferation. Catalase treatment did not prevent the above events nor the increased rate of apoptosis in the zinc-deficient cells. It is first demonstrated that a decrease in cellular zinc triggers H2O2-independent, as well as H2O2-dependent effects on MAPKs. Zinc deficiency-induced increases in cellular H2O2 can trigger the activation of JNK and p38, leading to AP-1 activation, events that are not involved in zinc deficiency-induced apoptosis. Antioxid. Redox Signal. 7, 1773–1782.