The Role of Zinc in the Modulation of Neuronal Proliferation and ApoptosisReport as inadecuate

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Neurotoxicity Research

, 17:1

First Online: 26 September 2009Received: 18 March 2009Revised: 13 May 2009Accepted: 17 May 2009


Although a requirement of zinc Zn for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons. This occurs in part as a consequence of decreased cell proliferation and increased apoptotic cell death. In IMR-32 cells, Zn deficiency led to the inhibition of cell proliferation through the arrest of the cell cycle at the G0-G1 phase. Zn deficiency induced apoptosis in both proliferating and quiescent neuronal cells via the intrinsic apoptotic pathway. Reductions in cellular Zn triggered a translocation of the pro-apoptotic protein Bad to the mitochondria, cytochrome c release, and caspase-3 activation. Apoptosis is the resultant of the inhibition of the prosurvival extracellular-signal-regulated kinase, the inhibition of nuclear factor-kappa B, and associated decreased expression of antiapoptotic proteins, and to a direct activation of caspase-3. A deficit of Zn during critical developmental periods can have persistent effects on brain function secondary to a deregulation of neuronal proliferation and apoptosis.

KeywordsZinc Neuron Proliferation Apoptosis Caspase Nuclear factor-kappa B NF-κB Extracellular-signal-regulated kinase ERK Zinc deficiency Cortical neuron Bad AbbreviationsCdksCyclin-dependent kinases

DTPADiethylenetriamine pentaacetic acid

EMSAElectrophoretic mobility shift assay

ERKExtracellular-signal-regulated kinase

FBSFetal bovine serum

MAPKMitogen-activated kinases

NF-κBNuclear factor-kappa B


Ana M. Adamo and Maria P. Zago contributed equally to this study.

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Author: Ana M. Adamo - Maria P. Zago - Gerardo G. Mackenzie - Lucila Aimo - Carl L. Keen - Alison Keenan - Patricia I. Oteiza



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