The general interest is osmotic regulation of gene expression. The model system is mammalian renal medullary cells. Because of the urinary concentrating mechanism, the renal medulla is the only mammalian tissue that is routinely exposed to hyperosmotic stress under normal physiologic conditions. The cells of the renal medulla are able to survive such stress because they can accumulate non-perturbing, osmotically active organic solutes (organic osmolytes) instead of perturbing inorganic ions. The five principal organic osmolytes are: sorbitol, glycerophosphocholine (GPC), betaine, inositol, and taurine. We worked on the original identification of the organic osmolytes and have elucidated the biochemical mechanisms by which they are accumulated. Hyperosmotic stress increases sorbitol synthesis by transcriptional induction of the gene for aldose reductase (AR). GPC degradation is osmotically regulated through its degradation. Betaine, inositol and taurine transport is increased by hyperosmolality. Transcriptional regulation of the transporter genes has been also demonstrated for betaine and inositol. Recently, we identified the first eukaryotic osmotic response element (ORE) in the AR gene (PNAS 91: 10742-10746, 1994). Currently, we have narrowed down the length of the minimal essential ORE necessary for osmotic response (JBC, in press). Future plans include the identification and characterization of transcription factors that interact with the ORE to elicit the response.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL001284-01
Application #
2441403
Study Section
Special Emphasis Panel (KE)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code