Serum or target deprivation-induced neuronal death causes oxidative neuronal accumulation of Zn2+ and loss of NAD+.

ABSTRACT: Trophic deprivation-mediated neuronal death is important during development, after acute brain or nerve trauma, and in neurodegeneration. Serum deprivation (SD) approximates trophic deprivation in vitro, and an in vivo model is provided by neuronal death in the mouse dorsal lateral geniculate nucleus (LGNd) after ablation of the visual cortex (VCA). Oxidant-induced intracellular Zn(2+) release ([Zn(2+) ](i) ) from metallothionein-3 (MT-III), mitochondria or 'protein Zn(2+) ', was implicated in trophic deprivation neurotoxicity. We have previously shown that neurotoxicity of extracellular Zn(2+) required entry, increased [Zn(2+) ](i) , and reduction of NAD(+) and ATP levels causing inhibition of glycolysis and cellular metabolism. Exogenous NAD(+) and sirtuin inhibition attenuated Zn(2+) ne

SUBMITTER: Sheline CT 

PROVIDER: S-EPMC2946389 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature