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Volume 272, Number 26, Issue of June 27, 1997 pp. 16431-16437
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification and Characterization of Multiple Osmotic Response Sequences in the Human Aldose Reductase Gene

(Received for publication, October 7, 1996, and in revised form, January 24, 1997)

Ben C. B. Ko , Barbara Ruepp ^§ , Kurt M. Bohren ^§ , Kenneth H. Gabbay ^§ and Stephen S. M. Chung

From the  Institute of Molecular Biology, The University of Hong Kong, 3/F, 8 Sassoon Road, Pokfulam, Hong Kong and the ^§ Molecular Diabetes and Metabolism Section, Departments of Pediatrics and Cell Biology, Baylor College of Medicine, Houston, Texas 77030

Aldose reductase (AR) has been implicated in osmoregulation in the kidney because it reduces glucose to sorbitol, which can serve as an osmolite. Under hyperosmotic stress, transcription of this gene is induced to increase the enzyme level. This mode of osmotic regulation of AR gene expression has been observed in a number of nonrenal cells as well, suggesting that this is a common response to hyperosmotic stress. We have identified a 132-base pair sequence ~1 kilobase pairs upstream of the transcription start site of the AR gene that enhances the transcription activity of the AR promoter as well as that of the SV40 promoter when the cells are under hyperosmotic stress. Within this 132-base pair sequence, there are three sequences that resemble TonE, the tonicity response element of the canine betaine transporter gene, and the osmotic response element of the rabbit AR gene, suggesting that the mechanism of osmotic regulation of gene expression in these animals is similar. However, our data indicate that cooperative interaction among the three TonE-like sequences in the human AR may be necessary for their enhancer function.

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