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MIOX  -  myo-inositol oxygenase

Homo sapiens

Synonyms: ALDRL6, Aldehyde reductase-like 6, Inositol oxygenase, KSP32, Kidney-specific protein 32, ...
 
 
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Disease relevance of MIOX

  • In the present study, extra-renal tissues and cell types, including those affected by diabetic complications, were examined for MIOX expression [1].
  • Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus [2].
  • To gain further insights into the molecular mechanisms involved in acute renal failure, we have isolated a new gene from rat and human, named KSP32 (kidney-specific protein with a molecular mass of 32 kDa) [3].
  • Finally, KSP32 mRNA was dramatically downregulated in rat following induction of acute ischemic renal failure [3].
 

High impact information on MIOX

  • myo-Inositol oxygenase (MIOX) activates O(2) at a mixed-valent nonheme diiron(II/III) cluster to effect oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)-ol substrate [myo-inositol (MI)] by four electrons to d-glucuronate [4].
  • The structure also reveals the basis of substrate specificity and suggests routes for the development of specific MIOX inhibitors [5].
  • Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism [5].
  • Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage reaction catalyzed by myo-inositol oxygenase [4].
  • These results suggest that the expression of MIOX is up-regulated by a positive feedback mechanism where xylitol, one of the products of MI catabolism via the glucuronate-xylulose pathway, induces an overexpression of MIOX [6].
 

Biological context of MIOX

 

Anatomical context of MIOX

  • Here we present evidence that the basis for the depletion of MI in diabetes is likely to be mediated by the increased expression of MIOX, which is induced by sorbitol, mannitol, and xylitol in a porcine renal proximal tubular epithelial cell line, LLC-PK1 [6].
  • In addition, quantitative real-time RT-PCR analysis of all major tissues in the mouse showed that the sciatic nerve contained MIOX transcript, which was found to be significantly higher than that observed in other non-renal organs [1].
  • Reverse-transcription-polymerase chain reaction (RT-PCR) and Western immunoblot analyses, however, revealed that the cell lines ARPE-19 and HLE-B3, representing human retinal pigmented epithelium and lens epithelium, respectively, also express MIOX [1].
  • In situ hybidization analysis revealed that the expression of KSP32 mRNA was prominent in the boundary of kidney cortex and outer medulla, exhibiting a raylike formation extending from the medulla into the cortex [3].
 

Associations of MIOX with chemical compounds

 

Other interactions of MIOX

 

Analytical, diagnostic and therapeutic context of MIOX

  • Based on luciferase reporter and electrophoretic mobility shift assays, polyols increased the ORE-dependent expression of MIOX [6].
  • Western blotting results indicated that kidney is the only major organ where MIOX protein is expressed at detectable levels [1].
  • 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 [2].

References

  1. Expression of myo-inositol oxygenase in tissues susceptible to diabetic complications. Arner, R.J., Prabhu, K.S., Krishnan, V., Johnson, M.C., Reddy, C.C. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  2. Gene regulation of aldose-, aldehyde- and a renal specific oxido reductase (RSOR) in the pathobiology of diabetes mellitus. Danesh, F.R., Wada, J., Wallner, E.I., Sahai, A., Srivastava, S.K., Kanwar, Y.S. Current medicinal chemistry. (2003) [Pubmed]
  3. Identification of a novel kidney-specific gene downregulated in acute ischemic renal failure. Hu, E., Chen, Z., Fredrickson, T., Gellai, M., Jugus, M., Contino, L., Spurr, N., Sims, M., Halsey, W., Van Horn, S., Mao, J., Sathe, G., Brooks, D. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  4. Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage reaction catalyzed by myo-inositol oxygenase. Xing, G., Diao, Y., Hoffart, L.M., Barr, E.W., Prabhu, K.S., Arner, R.J., Reddy, C.C., Krebs, C., Bollinger, J.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Crystal structure of a substrate complex of myo-inositol oxygenase, a di-iron oxygenase with a key role in inositol metabolism. Brown, P.M., Caradoc-Davies, T.T., Dickson, J.M., Cooper, G.J., Loomes, K.M., Baker, E.N. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Up-regulation of human myo-inositol oxygenase by hyperosmotic stress in renal proximal tubular epithelial cells. Prabhu, K.S., Arner, R.J., Vunta, H., Reddy, C.C. J. Biol. Chem. (2005) [Pubmed]
  7. A Coupled Dinuclear Iron Cluster that Is Perturbed by Substrate Binding in myo-Inositol Oxygenase. Xing, G., Hoffart, L.M., Diao, Y., Prabhu, K.S., Arner, R.J., Reddy, C.C., Krebs, C., Bollinger, J.M. Biochemistry (2006) [Pubmed]
  8. Oxygen Activation by a Mixed-Valent, Diiron(II/III) Cluster in the Glycol Cleavage Reaction Catalyzed by myo-Inositol Oxygenase. Xing, G., Barr, E.W., Diao, Y., Hoffart, L.M., Prabhu, K.S., Arner, R.J., Reddy, C.C., Krebs, C., Bollinger, J.M. Biochemistry (2006) [Pubmed]
  9. Concerning the mechanism for transfer of D-glucuronate from myo-inositol oxygenase to D-glucuronate reductase. Naber, N.I., Hamilton, G.A. Biochim. Biophys. Acta (1987) [Pubmed]
 
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