BibTeX
@ARTICLE{
         Seth2014Zdi,
       title = "Zinc deficiency induces apoptosis via mitochondrial p53- and caspase-dependent
         pathways in human neuronal precursor cells",
       author = "Rohit Seth",
       year = "2014",
       journal = "Journal of Trace Elements in Medicine and Biology",
       abstract = "Previous studies have shown that zinc deficiency leads to apoptosis of neuronal
         precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription
         factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the
         translocation of phosphorylated p53 to the mitochondria and p53-dependent increases in the
         pro-apoptotic mitochondrial protein BAX leading to a loss of mitochondrial membrane potential as
         demonstrated by a 25% decrease in JC-1 red:green fluorescence ratio. Disruption of mitochondrial
         membrane integrity was accompanied by efflux of the apoptosis inducing factor (AIF) from the
         mitochondria and translocation to the nucleus with a significant increase in reactive oxygen species
         (ROS) after 24 h of zinc deficiency. Measurement of caspase cleavage, mRNA, and treatment with
         caspase inhibitors revealed the involvement of caspases 2, 3, 6, and 7 in zinc deficiency-mediated
         apoptosis. Down-stream targets of caspase activation, including the nuclear structure protein lamin
         and polyADP ribose polymerase (PARP), which participates in DNA repair, were also cleaved.
         Transfection with a dominant-negative p53 construct and use of the p53 inhibitor, pifithrin-
         ␮, established that these alterations were largely dependent on p53. Together these data
         identify a cascade of events involving mitochondrial p53 as well as p53-dependent caspase-mediated
         mechanisms leading to apoptosis during zinc deficiency.",
       ad_area = "Metal Forming"
}