Relevance of aldo-keto reductase family members to the pathobiology of diabetic nephropathy and renal development

Aldo-keto reductases (AKRs) are a family of monomeric oxido-reductases with molecular weight ranging from 35-40 kDa and currently includes upwards of 60 members. They are expressed in a wide variety of tissues, where they cat alyze the NADPH-dependent reduction of various aliphatic and aromatic aldeh ydes and ketones. The functions of most of the family members are not well defined. But two members, aldehyde reductase (AKR1A) and aldose reductase ( AKR1B), have been extensively studied. The latter has received the most att ention since being relevant to the complications of diabetes mellitus: It i s upregulated during hyperglycemia, and at the same time there is an increa sed activity of the sorbitol pathway aAlthough, it has no homology with oth er AKR members, it binds to NADPH with high affinity and is up-regulated in streptozotocin-induced diabetes in mice. It is also developmentally regula ted and seems to selectively modulate renal tubulogenesis during embryonic life.nd non-enzymatic glycation of proteins with ensuing damage in various tissues. It is developmentally regulated in the ocular lens, and is believe d to modulate lens fiber morphogenesis during fetal life. Unlike the other AKR family members that are ubiquitously expressed, recently a renal-specif ic oxio-reductase has been described that. is expressed exclusively in the proximal tubules.