Gene Regulation of Aldose-, Aldehyde- and a Renal Specific Oxido Reductase (RSOR) in the Pathobiology of Diabetes Mellitus

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Abstract:

Aldose-, aldehyde and renal specific oxido reductase (RSOR) belong to the family of aldo-keto reductases (AKRs). They are monomeric (α / β)8-barrel proteins with a molecular weight ranging from 30 to 40 kDa, and at present include more than 60 members. Except for RSOR, they are expressed in a wide variety of animal and plant species and in various tissues. They catalyze NADPHdependent reduction of various aliphatic and aromatic aldehyde and ketones. During the past three decades aldehyde reductase (AKR1A) and aldose reductase (AKR1B) have been extensively investigated, and the gene regulation of AKR1B has been noted to be heavily influenced by hyperglycemic state and high glucose ambience in various culture systems. AKR1B catalyzes the conversion of glucose to sorbitol in concert with a coenzyme, NADPH. The newly discovered RSOR has certain structural and functional similarities to AKR1B and seems to be relevant to the renal complications of diabetes mellitus. Like other AKRs, it has a NADPH binding motif, however, it is located at the N-terminus and it probably undergoes N-linked glycosylation in order to achieve functional substrate specificity. Besides the AKR3 motif, it has very little nucleotide or protein sequence homology with other members of the AKR family. Nevertheless, gene regulation of RSOR, like AKR1B, is heavily modulated by carbonyl, oxidative and osmotic stresses, and thus it is anticipated that its discovery would lead to the development of new inhibitors as well as gene therapy targets to alleviate the complications of diabetes mellitus in the future.

Keywords: aldehyde reductase; aldo-keto reductases; gene regulation; pathobiology of diabetes mellitus; renal specific oxido reductase

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867033457368

Affiliations: Department of Pathology, Northwestern University Medical School, 303 E. Chicago Avenue, Chicago, Illinois 60611, USA.

Publication date: August 1, 2003

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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