Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus

Farhad R. Danesh, Jun Wada, Elizabeth I. Wallner, Atul Sahai, Satish Srivastava, Yashpal S. Kanwar

Research output: Contribution to journalArticle

4 Scopus citations

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 NADPH-dependent 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.

Original languageEnglish (US)
Pages (from-to)1399-1406
Number of pages8
JournalCurrent Medicinal Chemistry
Volume10
Issue number15
StatePublished - 2003

    Fingerprint

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Danesh, F. R., Wada, J., Wallner, E. I., Sahai, A., Srivastava, S., & Kanwar, Y. S. (2003). Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus. Current Medicinal Chemistry, 10(15), 1399-1406.