dc.contributor.author	Le, Nguyet
dc.contributor.author	Hufford, Timothy
dc.contributor.author	Park, Jong S.
dc.contributor.author	Brewster, Rachel
dc.date.accessioned	2021-11-10T18:58:49Z
dc.date.available	2021-11-10T18:58:49Z
dc.date.issued	2021-10-19
dc.description.abstract	Many organisms rely on oxygen to generate cellular energy (adenosine triphosphate or ATP). During severe hypoxia, the production of ATP decreases, leading to cell damage or death. Conversely, excessive oxygen causes oxidative stress that is equally damaging to cells. To mitigate pathological outcomes, organisms have evolved mechanisms to adapt to fluctuations in oxygen levels. Zebrafish embryos are remarkably hypoxia-tolerant, surviving anoxia (zero oxygen) for hours in a hypometabolic, energy-conserving state. To begin to unravel underlying mechanisms, we analyze here the distribution of the N-myc Downstream Regulated Gene (ndrg) family, ndrg1-4, and their transcriptional response to hypoxia. These genes have been primarily studied in cancer cells and hence little is understood about their normal function and regulation. We show here using in situ hybridization that ndrgs are expressed in metabolically demanding organs of the zebrafish embryo, such as the brain, kidney, and heart. To investigate whether ndrgs are hypoxia-responsive, we exposed embryos to different durations and severity of hypoxia and analyzed transcript levels. We observed that ndrgs are differentially regulated by hypoxia and that ndrg1a has the most robust response, with a ninefold increase following prolonged anoxia. We further show that this treatment resulted in de novo expression of ndrg1a in tissues where the transcript is not observed under normoxic conditions and changes in Ndrg1a protein expression post-reoxygenation. These findings provide an entry point into understanding the role of this conserved gene family in the adaptation of normal cells to hypoxia and reoxygenation.	en_US
dc.description.sponsorship	We acknowledge P. Chowdhary and B. Weinstein for their helpful comments on our manuscript. We would also like to acknowledge T. deCarvalho and S. Larson for imaging our samples during the COVID-19 pandemic that limited access to the Keith Porter Imaging Facility. This project was supported by funding from the Department of Defense (W81XWH-16-1-0466) and the National Institute of Health/NICHD (R21HD089476) to R. Brewster. N. Le was supported by a National Institute of Health /NIGMS MARC U*STAR (T34 HHS 00001) National Research Service Award to UMBC. T. Hufford was supported by CBI (NIGMS/NIH T32 GM066706) and IMSD (NIGMS/NIH T32 GM055036) training grants.	en_US
dc.description.uri	https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202100443R	en_US
dc.format.extent	4 files	en_US
dc.genre	journal articles	en_US
dc.identifier	doi:10.13016/m2tddk-fjjw
dc.identifier.citation	Le, Nguyet et al.; Differential expression and hypoxia-mediated regulation of the N-myc downstream regulated gene family; The Journal of the Federation of American Societies for Experimental Biology, 35, 11, 19 October, 2021; https://doi.org/10.1096/fj.202100443R	en_US
dc.identifier.uri	https://doi.org/10.1096/fj.202100443R
dc.identifier.uri	http://hdl.handle.net/11603/23306
dc.language.iso	en_US	en_US
dc.publisher	Wiley Online Library	en_US
dc.relation.isAvailableAt	The University of Maryland, Baltimore County (UMBC)
dc.relation.ispartof	UMBC Biological Sciences Department Collection
dc.relation.ispartof	UMBC Student Collection
dc.relation.ispartof	UMBC Faculty Collection
dc.rights	This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.	en_US
dc.rights	Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc/4.0/	*
dc.title	Differential expression and hypoxia-mediated regulation of the N-myc downstream regulated gene family	en_US
dc.type	Text	en_US
dcterms.creator	https://orcid.org/0000-0003-3003-5047	en_US
dcterms.creator	https://orcid.org/0000-0002-9058-2045	en_US

Differential expression and hypoxia-mediated regulation of the N-myc downstream regulated gene family

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