ArticleThe Journal of biological chemistry2009
ZAC1 is up-regulated by hypertonicity and decreases sorbitol dehydrogenase expression, allowing accumulation of sorbitol in kidney cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- A high-performance liquid chromatography-tandem mass spectrometry-based targeted metabolomics kidney dysfunction marker panel in human urine.Clinica chimica acta; international journal of clinical chemistry · 2015Article
- Opposing activity changes in AMP deaminase and AMP-activated protein kinase in the hibernating ground squirrel.PloS one · 2015Article
- Uric acid-dependent inhibition of AMP kinase induces hepatic glucose production in diabetes and starvation: evolutionary implications of the uricase loss in hominids.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Evolutionary history and metabolic insights of ancient mammalian uricases.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Counteracting roles of AMP deaminase and AMP kinase in the development of fatty liver.PloS one · 2012Article
- Effects of 2-bromoethanamine on TonEBP expression and its possible role in induction of renal papillary necrosis in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
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Authors and funding
6 authors at 1 institution in 1 country.
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Abstract
Affymetrix GeneChip technology was employed to detect differentially expressed genes in inner medullary collecting duct (IMCD3) cells grown under isotonic and hypertonic conditions. A marked up-regulation was found for the zinc-finger protein ZAC1 under hypertonic stress (219-fold, p < 0.001). Changes in expression for ZAC1 were verified by quantitative PCR for message and Western blotting for protein. In mouse and human kidney tissues, ZAC1 expression was substantial in the papilla and was absent in the cortex. Furthermore, ZAC1 expression significantly increased in the papilla of mice following 36 h of fluid restriction and decreased in polyuric mice consuming sucrose in water. Because ZAC1 has been described to be a potential negative regulator of sorbitol dehydrogenase (SDH) in hippocampal cells, we examined whether this relationship also occurs in kidney cells under hypertonic stress. We found that stable IMCD3 clones silenced for ZAC1 to varying levels demonstrated an inverse effect on SDH expression. ZAC1 binds to a consensus repression site within the promoter of SDH, pointing to a mechanism whereby ZAC1 acts by repressing SDH transcriptional activity during hypertonic conditions. Taken together, these data strongly suggest that ZAC1 is up-regulated under hypertonic stress and negatively regulates expression of SDH, allowing for accumulation of sorbitol as a compatible organic osmolyte.
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