by Richard Liang
The human body has developed mechanisms to deal with genetically damaged cells before they can become a threat. One such mechanism occurs when DNA is excessively damaged. Cells undergo cell death mediated by an enzyme known as poly ADP-ribose polymerase-1 (PARP-1). However, in certain instances like a stroke, the PARP-1 pathway is overly activated, causing mass cell death in the body. In a recent study led by Dr. Yingfei Wang at Johns Hopkins School of Medicine, the main enzyme in the PARP-1 mediated pathway was identified.
The enzyme identified in this study is known as Macrophage Migration Inhibitory Factor (MIF), an endonuclease in the PARP-1 pathway that cleaves the DNA in cells. 3-D modeling was used to determine the structure of MIF and exposing DNA to MIF tested its activity. When DNA was exposed to MIF, the DNA became cleaved, demonstrating the enzyme’s nuclease activity.
A mouse model was then exposed to an adeno-associated virus serotype 2 containing either a wild-type of MIF or an inactive version of MIF. The mice that were exposed to an inactive version of MIF retained an average of 75% more of their cortex, striatum, and hemisphere (regions of the brain) compared to the mice that were exposed to the active version of MIF. This showed that MIF was directly related to the PARP-1 pathway.
With further research into the activity of MIF in different conditions, the mass cell death induced by PARP-1 in certain diseases could be mitigated.
- Y. Wang, et al., A nuclease that mediates cell death by DNA damage and poly(ADP-ribose) polymerase-1. Science (2016).
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