The role of zinc in the modulation of neuronal proliferation and apoptosis

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 ce...

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Bibliographic Details
Authors: Adamo, Ana María, Zago, María Paola, Mackenzie, Gerardo G., Aimo, Lucila, Keen, Carl L., Keenan, Alison, Oteiza, Patricia Isabel
Format: article
Status:Published version
Publication Date:2010
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/97440
Online Access:http://hdl.handle.net/11336/97440
Access Level:Open access
Keyword:APOPTOSIS
BAD
CASPASE
CORTICAL NEURON
EXTRACELLULAR-SIGNAL-REGULATED KINASE (ERK)
NEURON
NUCLEAR FACTOR-KAPPA B (NF-ΚB)
PROLIFERATION
ZINC
ZINC DEFICIENCY
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Description
Summary: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.

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