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Gene Review

Cyb5r3  -  cytochrome b5 reductase 3

Mus musculus

Synonyms: 0610016L08Rik, 2500002N19Rik, B5R, C85115, Cytochrome b5 reductase, ...
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Disease relevance of Cyb5r3

  • Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity [1].
  • Residual nNOSbeta generates only 10% of the normal NO level in vitro but produces citrulline and diaphorase staining reflecting in vivo NOS activity in pelvic ganglion nerves that is comparable to WT animals [2].
  • Sequence data and PCR analysis indicated that m8 was a progeny of LO and that m8 preserved almost all of the open reading frames of vaccinia virus except for the disrupted EEV envelope gene B5R [3].
  • The data suggest that the B5R protein and the C-terminal region of the A33R protein are involved in adherence of cell-associated enveloped virions to cells [4].
  • Alterations in electrophoretic mobility, diaphorase activity, and terminal differentiation induced in murine erythroleukemia lines by differentiating agents [5].

Psychiatry related information on Cyb5r3

  • Given recent evidence that diaphorase- and cholinesterase-containing striatal neurons are selectively spared in Huntington's disease, our results strengthen the possibility that NMDA receptor-mediated neurotoxicity may participate in the pathogenesis of that disease [6].

High impact information on Cyb5r3

  • It is shown that the cellular reduction is an enzymatic process and that an oxygen-free and cell-free medium containing both the coenzyme NADH and the hydride transfer enzyme diaphorase is capable of reducing the dyes to the colorless leuko form.(ABSTRACT TRUNCATED AT 400 WORDS)[7]
  • A small proportion of neutral phospholipase A2 has the same repartition on the sucrose gradient as nicotinamide adenine dinucleotide diaphorase (EF, an endoplasmic reticulum marker, and as 5'-nucleotidase, a plasma membrane marker [8].
  • Thus, we identified Galpha12/13-proteins as essential components linking extracellular signals to localized Rho-Dia1 function during directed cell movement [9].
  • Knock down of Dia1 reveals its requirement for microtubule stabilization as well as polarized cell migration [9].
  • Enhanced expression of endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase reactivity in microvessels, as well as the presence of numerous inducible nitric oxide synthase-immunoreactive microglia, accompanied the increases in BBB permeability [10].

Chemical compound and disease context of Cyb5r3


Biological context of Cyb5r3


Anatomical context of Cyb5r3

  • Compartmentation of NADPH-diaphorase activity in the mouse cerebellar cortex [18].
  • As part of an 'enzyme-directed' approach to bioreductive drug development, we have measured the activity of NADH: cytochrome b5 reductase (B5R) in human cancer cell lines in order to assess the role of this enzyme in activating bioreductive drugs, and thus in influencing the cytotoxicity of these compounds [19].
  • In this study we have investigated the activity of quinone reductase (QR) (NADPH:DT diaphorase), a quinone detoxifying enzyme, in whole bone marrow and bone marrow-derived stromal cells from these two strains of mice [20].
  • RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1 [21].
  • Consistent with the results for eNOS mRNA and protein expression, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and eNOS immunoreactivity localized in the endothelium of the renal vasculature changed parallel with the amount of salt intake [22].

Associations of Cyb5r3 with chemical compounds

  • The unique activity had properties of a diaphorase but was distinct from NQOI because of a lack of correlation between NQOI (2,6-dichlorophenolindophenol reduction) activity and the amount of MMC-reductive activation leading to DNA cross-linking [23].
  • In the former we found that residual uninhibited activity remained in the presence of pHMB, in some cases accounting for up to 60% of the total reduction of cytochrome c. Thus, simply measuring the NADH-dependent reduction of cytochrome c consistently overestimated B5R activity [19].
  • The erythrocyte membrane was separated into Triton X-100-soluble and -insoluble fractions, and the detergent-soluble fraction was replaced by the soluble or membrane form of b5R (NADH-cytochrome b5 reductase) [24].
  • The molecular activity of the enzyme (approximately 500/min) is much lower than that reported for NADH-cytochrome b5 reductase, suggesting that the activity or amount of hydroxylase is rate-limiting in CMP-N-glycolylneuraminic acid (NeuGc) biosynthesis [25].
  • Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry revealed nitric oxide synthase only in the endothelium and media of graft arterioles in animals in the oldest age group [26].

Other interactions of Cyb5r3


Analytical, diagnostic and therapeutic context of Cyb5r3

  • Thus, mice vaccinated with 10(7) PFU of m8 produced low levels of anti-B5R antibodies after WR challenge, probably because of quick clearance of B5R-expressing WR EEV by strong immunity induced by the vaccination [3].
  • In the kidneys of AT1a-/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry [32].
  • Transmission electron microscopy indicated that INV particles were not wrapped by a double layer of Golgi-derived membrane and enveloped particles were not detected within the cell or on the cell surface without expression of the B5R protein [17].
  • Biochemical measurement of EEV formation, by labeling infected cells with [3H]thymidine followed by cesium chloride density gradient centrifugation of particles released from the cells 24 hr postinfection, showed that only 10% of WT levels of EEV were produced by I-delta B5R [17].
  • Finally, an ORF with 93.4% amino acid identity to vaccinia WR B5R is present in variola major virus strain Harvey and the B5R protein was shown by Western blotting to be expressed by all orthopoxviruses tested [17].


  1. Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity. Koh, J.Y., Peters, S., Choi, D.W. Science (1986) [Pubmed]
  2. Alternatively spliced neuronal nitric oxide synthase mediates penile erection. Hurt, K.J., Sezen, S.F., Champion, H.C., Crone, J.K., Palese, M.A., Huang, P.L., Sawa, A., Luo, X., Musicki, B., Snyder, S.H., Burnett, A.L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. An attenuated LC16m8 smallpox vaccine: analysis of full-genome sequence and induction of immune protection. Morikawa, S., Sakiyama, T., Hasegawa, H., Saijo, M., Maeda, A., Kurane, I., Maeno, G., Kimura, J., Hirama, C., Yoshida, T., Asahi-Ozaki, Y., Sata, T., Kurata, T., Kojima, A. J. Virol. (2005) [Pubmed]
  4. Identification of second-site mutations that enhance release and spread of vaccinia virus. Katz, E., Wolffe, E., Moss, B. J. Virol. (2002) [Pubmed]
  5. Alterations in electrophoretic mobility, diaphorase activity, and terminal differentiation induced in murine erythroleukemia lines by differentiating agents. Gascoyne, P.R., Becker, F.F. J. Cell. Physiol. (1990) [Pubmed]
  6. Cultured striatal neurons containing NADPH-diaphorase or acetylcholinesterase are selectively resistant to injury by NMDA receptor agonists. Koh, J.Y., Choi, D.W. Brain Res. (1988) [Pubmed]
  7. Phototoxicity, redox behavior, and pharmacokinetics of benzophenoxazine analogues in EMT-6 murine sarcoma cells. Cincotta, L., Foley, J.W., Cincotta, A.H. Cancer Res. (1993) [Pubmed]
  8. Phospholipases A1 and A2 in subcellular fractions and plasma membranes of Krebs II ascites cells. Record, M., Lloveras, J., Ribes, G., Douste-Blazy, D. Cancer Res. (1977) [Pubmed]
  9. Galpha12/13 is essential for directed cell migration and localized Rho-Dia1 function. Goulimari, P., Kitzing, T.M., Knieling, H., Brandt, D.T., Offermanns, S., Grosse, R. J. Biol. Chem. (2005) [Pubmed]
  10. Induction of nitric oxide synthase and microglial responses precede selective cell death induced by chronic impairment of oxidative metabolism. Calingasan, N.Y., Park, L.C., Calo, L.L., Trifiletti, R.R., Gandy, S.E., Gibson, G.E. Am. J. Pathol. (1998) [Pubmed]
  11. Deletion of the vaccinia virus B5R gene encoding a 42-kilodalton membrane glycoprotein inhibits extracellular virus envelope formation and dissemination. Wolffe, E.J., Isaacs, S.N., Moss, B. J. Virol. (1993) [Pubmed]
  12. Expression of NADH-cytochrome b5 reductase during dimethyl sulfoxide-induced differentiation of Friend erythroleukemia cells. Lostanlen, D., Kaplan, J.C. FEBS Lett. (1982) [Pubmed]
  13. Nitric oxide synthase and neuronal vulnerability in Parkinson's disease. Hunot, S., Boissière, F., Faucheux, B., Brugg, B., Mouatt-Prigent, A., Agid, Y., Hirsch, E.C. Neuroscience (1996) [Pubmed]
  14. Conserved autosomal syntenic group on mouse (MMU) chromosome 15 and human (HSA) chromosome 22: assignment of a gene for arylsulfatase A to MMU 15 and regional mapping of DIA1, ARSA, and ACO2 on HSA 22. Francke, U., Tetri, P., Taggart, R.T., Oliver, N. Cytogenet. Cell Genet. (1981) [Pubmed]
  15. Assignment of the gene for NADH diaphorase Dia-1 to Mouse chromosome 15. Taggart, R.T., Tetri, P., Francke, U. Somatic Cell Genet. (1980) [Pubmed]
  16. Selenium and drug metabolism--I. Multiple modulations of mouse liver enzymes. Reiter, R., Wendel, A. Biochem. Pharmacol. (1983) [Pubmed]
  17. The vaccinia virus 42-kDa envelope protein is required for the envelopment and egress of extracellular virus and for virus virulence. Engelstad, M., Smith, G.L. Virology (1993) [Pubmed]
  18. Compartmentation of NADPH-diaphorase activity in the mouse cerebellar cortex. Hawkes, R., Turner, R.W. J. Comp. Neurol. (1994) [Pubmed]
  19. Development and validation of a spectrophotometric assay for measuring the activity of NADH: cytochrome b5 reductase in human tumour cells. Barham, H.M., Inglis, R., Chinje, E.C., Stratford, I.J. Br. J. Cancer (1996) [Pubmed]
  20. Differences in quinone reductase activity in primary bone marrow stromal cells derived from C57BL/6 and DBA/2 mice. Twerdok, L.E., Trush, M.A. Res. Commun. Chem. Pathol. Pharmacol. (1990) [Pubmed]
  21. RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1. Fernandez-Borja, M., Janssen, L., Verwoerd, D., Hordijk, P., Neefjes, J. J. Cell. Sci. (2005) [Pubmed]
  22. Alterations in renal endothelial nitric oxide synthase expression by salt diet in angiotensin type-1a receptor gene knockout mice. Sato, K., Kihara, M., Hashimoto, T., Matsushita, K., Koide, Y., Tamura, K., Hirawa, N., Toya, Y., Fukamizu, A., Umemura, S. J. Am. Soc. Nephrol. (2004) [Pubmed]
  23. Non-enzymatic and enzymatic activation of mitomycin C: identification of a unique cytosolic activity. Joseph, P., Xu, Y., Jaiswal, A.K. Int. J. Cancer (1996) [Pubmed]
  24. Dihydroceramide:sphinganine C-4-hydroxylation requires Des2 hydroxylase and the membrane form of cytochrome b5. Enomoto, A., Omae, F., Miyazaki, M., Kozutsumi, Y., Yubisui, T., Suzuki, A. Biochem. J. (2006) [Pubmed]
  25. Biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates. Purification and characterization of the key enzyme of the cytidine monophospho-N-acetylneuraminic acid hydroxylation system. Kawano, T., Kozutsumi, Y., Kawasaki, T., Suzuki, A. J. Biol. Chem. (1994) [Pubmed]
  26. Blood flow regulation in the transplanted fetal endocrine pancreas. Acquisition of a nitric oxide-dependent glucose-induced increase in blood flow. Olle, K., Karlsten, R., Sundler, F., Jansson, L. Transplantation (1996) [Pubmed]
  27. Rat strain variations in liver cytosolic DT-diaphorase activity and possible significance of the trait in carcinogenesis by azo dyes. Horie, S., Ikeda, H., Tamai, N., Ohta, A. Comp. Biochem. Physiol., B (1989) [Pubmed]
  28. Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. Al-Shabrawey, M., El-Remessy, A., Gu, X., Brooks, S.S., Hamed, M.S., Huang, P., Caldwell, R.B. Mol. Vis. (2003) [Pubmed]
  29. Differential maturational patterns of nitric oxide synthase-I and NADPH diaphorase in functionally distinct cortical areas of the mouse cerebral cortex. Oermann, E., Bidmon, H.J., Mayer, B., Zilles, K. Anat. Embryol. (1999) [Pubmed]
  30. Specific pattern of nitric oxide synthase expression in glial cells after hippocampal injury. Stojkovic, T., Colin, C., Le Saux, F., Jacque, C. Glia (1998) [Pubmed]
  31. The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP-dependent pathways. Vacher, C.M., Hardin-Pouzet, H., Steinbusch, H.W., Calas, A., De Vente, J. Eur. J. Neurosci. (2003) [Pubmed]
  32. Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice. Kihara, M., Umemura, S., Sugaya, T., Toya, Y., Yabana, M., Kobayashi, S., Tamura, K., Kadota, T., Kishida, R., Murakami, K., Fukamizu, A., Ishii, M. Kidney Int. (1998) [Pubmed]
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