Role Of N-myc Downstream Regulated Genes Family In Low Oxygen Adaptation

Nguyet Le
Mentor: Rachel Brewster, Biological Sciences

Oxygen deprivation decreases ATP production dramatically. In humans, the loss of ATP in organs with high metabolic rate, such as the brain and kidney, can lead to cell death. However, zebrafish embryos enter a hypometabolic state that enables them to conserve ATP and survive for up to 50 hours without oxygen. Currently, the mechanisms that promote this hypometabolic state are unknown. Our previous mass-spectrometry study revealed a significant increase of lactate concentration in zebrafish under anoxia. Lactate was previously shown to stabilize N-myc Downstream Regulated 3 (NDRG3) in hypoxic cancer cells to promote angiogenesis and cell survival. We hypothesize that lactate/NDRG signaling could also be utilized in normal cells of the zebrafish embryo to arrest ATP-demanding processes and enhance survival. To address this, I investigated the mRNA distribution and transcriptional regulation of NDRG family members. In situ hybridization revealed that NDRGs are enriched in the brain and kidney and expanded to other tissues such as the olfacoty placode and vasculature in response to anoxia. RT-qPCR revealed both up- and down-regulation of different NDRG members in response to anoxia. These studies will shed light on how NDRG family members contribute to low oxygen adaptation in normal cells of an intact organism.

This investigation was sponsored by NIH/NIGMS MARC U*STAR T3408663 National Research Service Award to UMBC.