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

Ana M. Adamo, Maria P. Zago, Gerardo Mackenzie, Lucila Aimo, Carl L Keen, Alison Keenan, Patricia I. Oteiza

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalNeurotoxicity Research
Volume17
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Apoptosis
  • Bad
  • Caspase
  • Cortical neuron
  • Extracellular-signal-regulated kinase (ERK)
  • Neuron
  • Nuclear factor-kappa B (NF-κB)
  • Proliferation
  • Zinc
  • Zinc deficiency

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Fingerprint Dive into the research topics of 'The role of zinc in the modulation of neuronal proliferation and apoptosis'. Together they form a unique fingerprint.

Cite this