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Previously it was reported that zinc deficiency leads to the apoptosis of human neuronal precursor cells in both in vivo and in-vitro studies. But in a recent study, a team of researchers from the Department of Biomedical Sciences, College of Medicine, Florida State University, USA, found out a molecular link between the zinc deficiency and apoptosis of the human neuronal precursor cells.
Zinc also plays an important role in the immune system and inflammatory responses while zinc deficiency is also related to different types of cancer.
p53 is a tumor suppressor protein that acts as a DNA binding transcription factor during zinc deficiency. Its phosphorylated form is translocated into the mitochondria where it causes an increase in pro-apoptotic mitochondrial proteins such as BAX. Increased production of BAX leads to the loss of mitochondrial membrane and disruption of the mitochondrial membrane integrity causes efflux of the apoptosis-inducing factor (AIF) from the mitochondria. Apoptosis-inducing factor released from the mitochondria is translocated into the nucleus and aids the production of Reactive Oxygen Species (ROS).
Researchers have measured the different type cleavage of caspases, and the amount of mRNA of caspases and BAX. Researchers have also studied the effect of caspase and BAX inhibitors and found increased mRNA expression of the BAX in the zinc-deficient neuronal precursor cells while treatment with mitochondrial p53 inhibitor µPFT prevented the BAX expression as well as the production of Reactive Oxygen Species. Furthermore, the treatment of the zinc-deficient neuronal precursor cells with ZVAD or µPFT also prevents the nuclear accumulation of the apoptosis-inducing factor by 50-70%.
Then, researchers performed initial RT-PCR analysis that reveals that zinc deficiency results in an increase in the mRNA level of the caspase 2, 3 and 7 while western blotting analysis reveals the link between zinc deficiency with an increase in the expression of caspase 3, 6 and 7. When inhibiting the p53 by ZVAD they observed the prevention of the activation of caspases that were activated by the cleavage of polyADP-ribose polymerase (PARP) and lamin.
In conclusion, zinc is an essential trace element that is required not only for the survival of neuronal precursor cells but also enables us to build up a model to describe the current understanding of the p53-dependent mechanism associated with the zinc deficiency-induced apoptosis.
Reference: Journal of Trace Elements in Medicine and Biology
Article DOI: 10.1016/j.jtemb.2014.10.010