ORE, a eukaryotic minimal essential osmotic response element. The aldose reductase gene in hyperosmotic stress

Organisms, almost universally, adapt to hyperosmotic stress through increased accumulation of organic osmolytes but the molecular mechanisms have only begun to be addressed. Among mammalian tissues, renal medullary cells are uniquely exposed to extreme hyperosmotic stress. Sorbitol, synthesized thro...

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Bibliographic Details
Published in:The Journal of biological chemistry 1996-08, Vol.271 (31), p.18318-18321
Main Authors: Ferraris, J D, Williams, C K, Jung, K Y, Bedford, J J, Burg, M B, García-Pérez, A
Format: Article
Language:English
Subjects:
Aldehyde Reductase - genetics
Aldehyde Reductase - metabolism
Animals
Base Sequence
Cell Line
Cloning, Molecular
Consensus Sequence
DNA - genetics
Dogs
Gene Expression Regulation
Genes, Reporter
Luciferases - genetics
Molecular Sequence Data
NF-kappa B - genetics
Osmotic Pressure
Rabbits
Sorbitol - metabolism
Transfection
Water-Electrolyte Balance - genetics
Water-Electrolyte Balance - physiology
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Summary:Organisms, almost universally, adapt to hyperosmotic stress through increased accumulation of organic osmolytes but the molecular mechanisms have only begun to be addressed. Among mammalian tissues, renal medullary cells are uniquely exposed to extreme hyperosmotic stress. Sorbitol, synthesized through aldose reductase, is a predominant osmolyte induced under hyperosmotic conditions in renal cells. Using a rabbit renal cell line, we originally demonstrated that hyperosmotic stress induces transcription of the aldose reductase gene. Recently, we cloned the rabbit aldose reductase gene, characterized its structure, and found the first evidence of an osmotic response region in a eukaryotic gene. Now, we have progressively subdivided this 3221-base pair (bp) region into discrete fragments in reporter gene constructs. Thereby, we have functionally defined the smallest sequence able to confer hyperosmotic response on a downstream gene independent of other putative cis-elements, that is, a minimal essential osmotic response element (ORE). The sequence of the ORE is CGGAAAATCAC(C) (bp -1105/-1094). A 17-bp fragment (-1108/-1092) containing the ORE used as a probe in electrophoretic mobility shift assays suggests hyperosmotic induction of a slowly migrating band. Isolation of trans-acting factor(s) and characterization of their interaction with the ORE should elucidate the basic mechanisms for regulation of gene expression by hyperosmotic stress.
ISSN:0021-9258
DOI:10.1074/jbc.271.31.18318