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(Received for publication, March 8, 1996, and in revised form, April 19, 1996)
From the Laboratory of Kidney and Electrolyte Metabolism, NHLBI,
National Institutes of Health, Bethesda, Maryland 20892-1598
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
Volume 271, Number 31,
Issue of August 2, 1996
pp. 18318-18321
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
COMMUNICATION:
THE ALDOSE REDUCTASE GENE IN HYPEROSMOTIC STRESS
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.
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