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Gene Review

Akr1b3  -  aldo-keto reductase family 1, member B3...

Mus musculus

Synonyms: ALR2, AR, Ahr-1, Ahr1, Akr1b1, ...
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Disease relevance of Akr1b3

  • These findings indicate that AR is responsible for the early events in the pathogenesis of diabetic retinopathy, leading to a cascade of retinal lesions, including blood-retinal barrier breakdown, loss of pericytes, neuro-retinal apoptosis, glial reactivation, and neovascularization [1].
  • Aldose reductase mRNA expression (a gene upregulated by medullary hyperosmolarity) increased in normal mice, but remained low in the cystic kidney, suggesting the absence of a hypertonic medullary interstitium [2].
  • Aldose reductase (AR), best known as the first enzyme in the polyol pathway of sugar metabolism, has been implicated in a wide variety of physiological functions and in the etiology of diabetic complications [3].
  • Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy [4].
  • Collectively, these data provide evidence that inhibition of AR may be a significant therapeutic approach in preventing bacterial endotoxin-induced sepsis and tissue damage [5].

Psychiatry related information on Akr1b3

  • The effects of dexmedetomidine, a subtype-nonselective alpha 2-AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the alpha 2C-AR gene and in their controls, but the hypothermic effect of the alpha 2-AR agonist was significantly attenuated by the receptor gene inactivation [6].

High impact information on Akr1b3


Chemical compound and disease context of Akr1b3


Biological context of Akr1b3


Anatomical context of Akr1b3


Associations of Akr1b3 with chemical compounds

  • AHR-A2 exhibited a defined specificity toward p-nitrobenzaldehyde as substrate, whereas the other enzymes exhibited broad specificities toward various aliphatic, aromatic, and monosaccharide aldehydes [16].
  • Evidence is presented for two new forms of mouse liver and kidney aldehyde reductase activity (designated AHR-3 and AHR-4) resolved using cellulose acetate electrophoresis zymogram techniques and stained by glyceraldehyde and NADPH as substrate and coenzyme, respectively [15].
  • No recombinants were observed between Adh-3 (encoding alcohol dehydrogenase C2; ADH-C2) and Ahr-1 among 42 backcross animals [16].
  • Using transgenic mice that overexpress aldose reductase (AR) in their lenses, we found that the flux of glucose through the polyol pathway is the major cause of hyperglycemic oxidative stress in this tissue [19].
  • In renal medullary cells, AR also plays an osmoregulatory role by accumulating sorbitol to maintain the intracellular osmotic balance during antidiuresis [20].

Physical interactions of Akr1b3

  • The FR-1 ternary complex structure indicates that it uses the same general catalytic mechanism as aldose reductase and other members of the family whose structures have been determined [21].

Regulatory relationships of Akr1b3


Other interactions of Akr1b3


Analytical, diagnostic and therapeutic context of Akr1b3


  1. Aldose reductase deficiency prevents diabetes-induced blood-retinal barrier breakdown, apoptosis, and glial reactivation in the retina of db/db mice. Cheung, A.K., Fung, M.K., Lo, A.C., Lam, T.T., So, K.F., Chung, S.S., Chung, S.K. Diabetes (2005) [Pubmed]
  2. Developmental expression of urine concentration-associated genes and their altered expression in murine infantile-type polycystic kidney disease. Gattone, V.H., Maser, R.L., Tian, C., Rosenberg, J.M., Branden, M.G. Dev. Genet. (1999) [Pubmed]
  3. Comparisons of genomic structures and chromosomal locations of the mouse aldose reductase and aldose reductase-like genes. Ho, H.T., Jenkins, N.A., Copeland, N.G., Gilbert, D.J., Winkles, J.A., Louie, H.W., Lee, F.K., Chung, S.S., Chung, S.K. Eur. J. Biochem. (1999) [Pubmed]
  4. Aldose reductase-deficient mice develop nephrogenic diabetes insipidus. Ho, H.T., Chung, S.K., Law, J.W., Ko, B.C., Tam, S.C., Brooks, H.L., Knepper, M.A., Chung, S.S. Mol. Cell. Biol. (2000) [Pubmed]
  5. Aldose Reductase Mediates the Lipopolysaccharide-induced Release of Inflammatory Mediators in RAW264.7 Murine Macrophages. Ramana, K.V., Fadl, A.A., Tammali, R., Reddy, A.B., Chopra, A.K., Srivastava, S.K. J. Biol. Chem. (2006) [Pubmed]
  6. Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist. Sallinen, J., Link, R.E., Haapalinna, A., Viitamaa, T., Kulatunga, M., Sjöholm, B., Macdonald, E., Pelto-Huikko, M., Leino, T., Barsh, G.S., Kobilka, B.K., Scheinin, M. Mol. Pharmacol. (1997) [Pubmed]
  7. Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. Vikramadithyan, R.K., Hu, Y., Noh, H.L., Liang, C.P., Hallam, K., Tall, A.R., Ramasamy, R., Goldberg, I.J. J. Clin. Invest. (2005) [Pubmed]
  8. Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis. Rittner, H.L., Hafner, V., Klimiuk, P.A., Szweda, L.I., Goronzy, J.J., Weyand, C.M. J. Clin. Invest. (1999) [Pubmed]
  9. Endotoxin-induced cardiomyopathy and systemic inflammation in mice is prevented by aldose reductase inhibition. Ramana, K.V., Willis, M.S., White, M.D., Horton, J.W., DiMaio, J.M., Srivastava, D., Bhatnagar, A., Srivastava, S.K. Circulation (2006) [Pubmed]
  10. Aldose reductase regulates growth factor-induced cyclooxygenase-2 expression and prostaglandin e2 production in human colon cancer cells. Tammali, R., Ramana, K.V., Singhal, S.S., Awasthi, S., Srivastava, S.K. Cancer Res. (2006) [Pubmed]
  11. A delayed-early gene activated by fibroblast growth factor-1 encodes a protein related to aldose reductase. Donohue, P.J., Alberts, G.F., Hampton, B.S., Winkles, J.A. J. Biol. Chem. (1994) [Pubmed]
  12. Characterization of a novel aldose reductase inhibitor, TAT, and its effects on streptozotocin-induced diabetic neuropathy in rats. Inukai, S., Agata, M., Sato, M., Naitou, A., Matsukawa, H., Goto, M. Jpn. J. Pharmacol. (1993) [Pubmed]
  13. Effect of fructose supplementation on sorbitol accumulation and myo-inositol metabolism in cultured neuroblastoma cells exposed to increased glucose concentrations. Yorek, M.A., Dunlap, J.A., Leeney, E.M., Stefani, M.R. J. Neurochem. (1990) [Pubmed]
  14. Differential control of murine aldose reductase and fibroblast growth factor (FGF)-regulated-1 gene expression in NIH 3T3 cells by FGF-1 treatment and hyperosmotic stress. Hsu, D.K., Guo, Y., Peifley, K.A., Winkles, J.A. Biochem. J. (1997) [Pubmed]
  15. Aldehyde reductase isozymes in the mouse: evidence for two new loci and localization of Ahr-3 on chromosome 7. Mather, P.B., Holmes, R.S. Biochem. Genet. (1985) [Pubmed]
  16. Biochemical genetics of aldehyde reductase in the mouse: Ahr-1--a new locus linked to the alcohol dehydrogenase gene complex on chromosome 3. Duley, J.A., Holmes, R.S. Biochem. Genet. (1982) [Pubmed]
  17. Presence of a closely related subgroup in the aldo-ketoreductase family of the mouse. Gui, T., Tanimoto, T., Kokai, Y., Nishimura, C. Eur. J. Biochem. (1995) [Pubmed]
  18. Characterization of the mouse aldose reductase gene and promoter in a lens epithelial cell line. McGowan, M.H., Iwata, T., Carper, D.A. Mol. Vis. (1998) [Pubmed]
  19. Contributions of polyol pathway to oxidative stress in diabetic cataract. Lee, A.Y., Chung, S.S. FASEB J. (1999) [Pubmed]
  20. Isolation of the mouse aldose reductase promoter and identification of a tonicity-responsive element. Daoudal, S., Tournaire, C., Halere, A., Veyssière, G., Jean, C. J. Biol. Chem. (1997) [Pubmed]
  21. 1.7 A structure of FR-1, a fibroblast growth factor-induced member of the aldo-keto reductase family, complexed with coenzyme and inhibitor. Wilson, D.K., Nakano, T., Petrash, J.M., Quiocho, F.A. Biochemistry (1995) [Pubmed]
  22. Steroidogenic factor-1 controls the aldose reductase akr1b7 gene promoter in transgenic mice through an atypical binding site. Martinez, A., Val, P., Sahut-Barnola, I., Aigueperse, C., Veyssière, G., Lefrançois-Martinez, A.M. Endocrinology (2003) [Pubmed]
  23. Sequential expression of NKCC2, TonEBP, aldose reductase, and urea transporter-A in developing mouse kidney. Lee, H.W., Kim, W.Y., Song, H.K., Yang, C.W., Han, K.H., Kwon, H.M., Kim, J. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  24. Identification of genes differentially expressed in vascular smooth muscle cells following benzo[a]pyrene challenge: implications for chemical atherogenesis. Lu, K.P., Ramos, K.S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  25. Aldose reductase inhibitors improve myocardial reperfusion injury in mice by a dual mechanism. Iwata, K., Matsuno, K., Nishinaka, T., Persson, C., Yabe-Nishimura, C. J. Pharmacol. Sci. (2006) [Pubmed]
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