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Gene Review

AKR1B1  -  aldo-keto reductase family 1, member B1...

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Disease relevance of AKR1B1


Psychiatry related information on AKR1B1

  • This dramatic change in stereospecificity may account for the reported apparent cooperative behavior exhibited also by highly purified electrophoretically homogeneous preparations of aldose reductase [6].

High impact information on AKR1B1

  • Three seemingly independent biochemical pathways are involved in the pathogenesis: glucose-induced activation of protein kinase C isoforms; increased formation of glucose-derived advanced glycation end-products; and increased glucose flux through the aldose reductase pathway [7].
  • These components include a recognition unit or receptor (for example, the beta-adrenergic receptor (beta AR) for catecholamines or the 'light receptor' rhodopsin), a guanine nucleotide regulatory or transducing protein, and an effector enzyme (for example, adenylate cyclase or cyclic GMP phosphodiesterase) [8].
  • Elevating glucose concentration in culture media from 100 to 400 mg/dl led to a 100% increase in sorbitol levels, which could be inhibited completely by sorbinil, an aldose reductase inhibitor [9].
  • Elevated cellular sorbitol levels resulting from conversion of increased glucose by aldose reductase might deplete cellular myoinositol content, which could then lower inositol phosphates (InsPs) and diacylglycerol levels, key regulators of protein kinase C (PKC) [9].
  • Thiamine and benfotiamine reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and intracellular glucose while increasing the expression and activity of transketolase, for which it is a coenzyme, in human endothelial cells and bovine retinal pericytes cultured in high glucose [10].

Chemical compound and disease context of AKR1B1


Biological context of AKR1B1


Anatomical context of AKR1B1

  • Despite the absence of a typical signal sequence, the human aldose reductase is partially translocated into the periplasm of the E. coli cells, where it is present in an enzymatically active form [2].
  • In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina [19].
  • Immunohistochemical localization of aldose reductase. I. Enzyme purification and antibody preparation--localization in peripheral nerve, artery, and testis [20].
  • All three aldose reductase inhibitors completely prevented or markedly reduced these hemodynamic and vascular filtration changes and increases in tissue sorbitol levels in the anterior uvea, posterior uvea, retina, sciatic nerve, and granulation tissue [21].
  • The addition of an aldose reductase inhibitor (ICI-128436, Statil) did not significantly affect the high-glucose-induced reduction of D-alpha-tocopherol binding, although it reduced sorbitol levels in the cells compared with those from cells cultured in high concentrations of glucose [22].

Associations of AKR1B1 with chemical compounds


Other interactions of AKR1B1


Analytical, diagnostic and therapeutic context of AKR1B1


  1. Molecular cloning of testicular 20 alpha-hydroxysteroid dehydrogenase: identity with aldose reductase. Warren, J.C., Murdock, G.L., Ma, Y., Goodman, S.R., Zimmer, W.E. Biochemistry (1993) [Pubmed]
  2. Cloning and prokaryotic expression of a biologically active human placental aldose reductase. Grundmann, U., Bohn, H., Obermeier, R., Amann, E. DNA Cell Biol. (1990) [Pubmed]
  3. The effect of aminoguanidine and tolrestat on glucose toxicity in bovine retinal capillary pericytes. Chibber, R., Molinatti, P.A., Wong, J.S., Mirlees, D., Kohner, E.M. Diabetes (1994) [Pubmed]
  4. Non-tryptophan fluorescence and high molecular weight protein formation in lens crystallins of rats with chronic galactosemia: prevention by the aldose reductase inhibitor sorbinil. Nagaraj, R.H., Monnier, V.M. Exp. Eye Res. (1990) [Pubmed]
  5. Quantitative structure-activity analysis of 5-arylidene-2,4-thiazolidinediones as aldose reductase inhibitors. Sambasivarao, S.V., Soni, L.K., Gupta, A.K., Hanumantharao, P., Kaskhedikar, S.G. Bioorg. Med. Chem. Lett. (2006) [Pubmed]
  6. Change in stereospecificity of bovine lens aldose reductase modified by oxidative stress. Del Corso, A., Barsacchi, D., Giannessi, M., Tozzi, M.G., Camici, M., Mura, U. J. Biol. Chem. (1989) [Pubmed]
  7. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nishikawa, T., Edelstein, D., Du, X.L., Yamagishi, S., Matsumura, T., Kaneda, Y., Yorek, M.A., Beebe, D., Oates, P.J., Hammes, H.P., Giardino, I., Brownlee, M. Nature (2000) [Pubmed]
  8. Light-dependent phosphorylation of rhodopsin by beta-adrenergic receptor kinase. Benovic, J.L., Mayor, F., Somers, R.L., Caron, M.G., Lefkowitz, R.J. Nature (1986) [Pubmed]
  9. Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. Lee, T.S., MacGregor, L.C., Fluharty, S.J., King, G.L. J. Clin. Invest. (1989) [Pubmed]
  10. Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose. Berrone, E., Beltramo, E., Solimine, C., Ape, A.U., Porta, M. J. Biol. Chem. (2006) [Pubmed]
  11. Aldose reductase: a window to the treatment of diabetic complications? Crabbe, M.J., Goode, D. Progress in retinal and eye research. (1998) [Pubmed]
  12. Spiro hydantoin aldose reductase inhibitors. Sarges, R., Schnur, R.C., Belletire, J.L., Peterson, M.J. J. Med. Chem. (1988) [Pubmed]
  13. Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Stribling, D., Mirrlees, D.J., Harrison, H.E., Earl, D.C. Metab. Clin. Exp. (1985) [Pubmed]
  14. Properties of novel aldose reductase inhibitors, M16209 and M16287, in comparison with known inhibitors, ONO-2235 and sorbinil. Kato, K., Nakayama, K., Mizota, M., Miwa, I., Okuda, J. Chem. Pharm. Bull. (1991) [Pubmed]
  15. Diagnosis of Salmonella bacteria: antibodies against synthetic Salmonella O-antigen 8 for immunofluorescence and co-agglutination using sensitized protein A-containing staphylococci. Svenungsson, B., Lindberg, A.A. Acta pathologica et microbiologica Scandinavica. Section B, Microbiology. (1979) [Pubmed]
  16. An aldose reductase with 20 alpha-hydroxysteroid dehydrogenase activity is most likely the enzyme responsible for the production of prostaglandin f2 alpha in the bovine endometrium. Madore, E., Harvey, N., Parent, J., Chapdelaine, P., Arosh, J.A., Fortier, M.A. J. Biol. Chem. (2003) [Pubmed]
  17. Sequence analysis of bovine lens aldose reductase. Schade, S.Z., Early, S.L., Williams, T.R., Kézdy, F.J., Heinrikson, R.L., Grimshaw, C.E., Doughty, C.C. J. Biol. Chem. (1990) [Pubmed]
  18. The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases. Bohren, K.M., Bullock, B., Wermuth, B., Gabbay, K.H. J. Biol. Chem. (1989) [Pubmed]
  19. Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications. Obrosova, I.G., Pacher, P., Szabó, C., Zsengeller, Z., Hirooka, H., Stevens, M.J., Yorek, M.A. Diabetes (2005) [Pubmed]
  20. Immunohistochemical localization of aldose reductase. I. Enzyme purification and antibody preparation--localization in peripheral nerve, artery, and testis. Ludvigson, M.A., Sorenson, R.L. Diabetes (1980) [Pubmed]
  21. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Tilton, R.G., Chang, K., Pugliese, G., Eades, D.M., Province, M.A., Sherman, W.R., Kilo, C., Williamson, J.R. Diabetes (1989) [Pubmed]
  22. High glucose reduces specific binding for D-alpha-tocopherol in cultured aortic endothelial cells. Kunisaki, M., Umeda, F., Yamauchi, T., Masakado, M., Nawata, H. Diabetes (1993) [Pubmed]
  23. Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. Pawlowski, J.E., Huizinga, M., Penning, T.M. J. Biol. Chem. (1991) [Pubmed]
  24. Cloning and sequence determination of human placental aldose reductase gene. Chung, S., LaMendola, J. J. Biol. Chem. (1989) [Pubmed]
  25. Aldose reductase inhibitor fidarestat prevents retinal oxidative stress and vascular endothelial growth factor overexpression in streptozotocin-diabetic rats. Obrosova, I.G., Minchenko, A.G., Vasupuram, R., White, L., Abatan, O.I., Kumagai, A.K., Frank, R.N., Stevens, M.J. Diabetes (2003) [Pubmed]
  26. Thiol/disulfide interconversion in bovine lens aldose reductase induced by intermediates of glutathione turnover. Vilardo, P.G., Scaloni, A., Amodeo, P., Barsotti, C., Cecconi, I., Cappiello, M., Lopez Mendez, B., Rullo, R., Dal Monte, M., Del Corso, A., Mura, U. Biochemistry (2001) [Pubmed]
  27. Regulation of glucose transporter (GLUT 3) and aldose reductase mRNA inbovine retinal endothelial cells and retinal pericytes in high glucose and high galactose culture. Knott, R.M., Robertson, M., Forrester, J.V. Diabetologia (1993) [Pubmed]
  28. Sorbinil prevents the galactose-induced inhibition of prostaglandin synthesis in lens cells. Cammarata, P.R., Jackson, T., Yorio, T. Invest. Ophthalmol. Vis. Sci. (1988) [Pubmed]
  29. Polyol pathway in human epididymis and semen. Frenette, G., Thabet, M., Sullivan, R. J. Androl. (2006) [Pubmed]
  30. Effect of bovine small intestine thioredoxin on aldose reductase activity. Mizoguchi, T., Maeda, I., Yagi, K., Kador, P.F. Chem. Biol. Interact. (2001) [Pubmed]
  31. Adrenodoxin reductase. Properties of the complexes of reduced enzyme with NADP+ and NADPH. Lambeth, J.D., Kamin, H. J. Biol. Chem. (1976) [Pubmed]
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