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Mb  -  myoglobin

Mus musculus

Synonyms: AI325109, Myoglobin
 
 
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Disease relevance of Mb

 

High impact information on Mb

  • Myoglobin, an intracellular haemoprotein expressed in the heart and oxidative skeletal myofibres of vertebrates, binds molecular oxygen and may facilitate oxygen transport from erythrocytes to mitochondria, thereby maintaining cellular respiration during periods of high physiological demand [6].
  • Here we show, however, that mice without myoglobin, generated by gene-knockout technology, are fertile and exhibit normal exercise capacity and a normal ventilatory response to low oxygen levels (hypoxia) [6].
  • Two more groups of hybridomas isolated from DBA/2 and B10.D2 mice immunized with myoglobin also recognized peptide 110-121 presented by E alpha d A beta d [7].
  • The T cell receptor repertoire influences V beta element usage in response to myoglobin [8].
  • Spleen dendritic cells and cultured epidermal Langerhans cells (LC) presented native myoglobin weakly and often not at all [9].
 

Chemical compound and disease context of Mb

  • This role depends on the reversible binding of O2 by Mb depending on PO2, which results in: (1) storage of O2; (2) buffering of PO2 in the cell to prevent mitochondrial anoxia; and (3) parallel diffusion of O2 (so-called, 'facilitated diffusion') [10].
  • The ESI-MS spectrum of the soluble fraction used in the toxicity tests, demonstrated that conjugation of T2N with Mb yielded Mb adducts with one residue of trans-2-nonenal per myoglobin molecule as the major fraction and adducts with different numbers of T2N molecules as minor fractions [11].
  • Furthermore, treatment of infected epithelial cells with 50 microM of the NO donor, S-nitroso-L-glutathione, resulted in significant inhibition (approximately 70%) of chlamydial multiplication, while the NO scavenger, myoglobin plus ascorbate, could reverse the effect, demonstrating that NO could directly inhibit human strains of Chlamydia [12].
 

Biological context of Mb

  • Here we report that Mb also significantly contributes to the attenuation of oxidative stress in cardiac muscle [13].
  • These results suggest that the role of Mb as an intracellular NO scavenger is small, and the increase in mitochondrial superoxide in SODHZ mice may cause a decrease NO bioavailability and alter the control of myocardial O2 consumption by NO [14].
  • In addition, we have defined blocks of conserved sequences in the 5' flanking region by comparison with other mammalian Mb genes [15].
  • Seal myoglobin (Mb) exons 1 and 3 were used as probes to isolate the functional mouse Mb gene [15].
  • Loss of Mb results in a distinct phenotype, even under resting conditions, and the importance of oxygen supply and nitric oxide scavenging by Mb is clearly demonstrated at the conscious animal level [16].
 

Anatomical context of Mb

  • We propose that Mb is a key element influencing redox pathways in cardiac muscle to functionally and metabolically protect the heart from oxidative damage [13].
  • Kidney cortex was studied as the negative control because it does not contain Mb [14].
  • This gene has a very low level of Mb expression in skeletal muscle [15].
  • Prior studies using transient transfection assays in cultured avian and murine skeletal myotubes indicate that the proximal 2-kb segment of the 5' flanking region of the human myoglobin gene contains transcriptional control elements sufficient to direct muscle-specific and developmentally regulated expression of reporter genes [17].
  • A distinctive spatial pattern of myoglobin promoter activity was observed in fetal hearts: beta-gal staining was more pronounced within the left ventricular subendocardium than within the subepicardium and was essentially undetectable in the ventricular trabeculae or atria [17].
 

Associations of Mb with chemical compounds

  • Although the primary function of myoglobin (Mb) has been considered to be cellular O2 storage and supply, recent studies have shown that Mb in addition can act as NO oxidase [13].
  • Mouse myoglobin possesses several features unique among all known myoglobins (Gly 31, Cys 66, Thr 74 and Glu 113) and one substitution unique among known mammalian myoglobins (Glu 53) [18].
  • Here we report that lack of myoglobin causes a biochemical shift in cardiac substrate utilization from fatty acid to glucose oxidation [19].
  • Individual T cell clones proliferated in response to one of three CNBr fragments of Mb [20].
  • (1)H NMR spectroscopy was used to measure directly the conversion of oxygenated Mb (MbO(2)) to metmyoglobin (metMb) by reaction with NO [21].
 

Physical interactions of Mb

 

Regulatory relationships of Mb

 

Other interactions of Mb

 

Analytical, diagnostic and therapeutic context of Mb

  • Expression of endogenous myoglobin mRNA and protein, assessed by in situ hybridization and immunohistochemistry, demonstrated a similar spatial pattern [17].
  • Using germ-line transgenesis and somatic cell gene transfer methods, we defined discrete regions of the murine and human genes encoding myoglobin that are sufficient to confer muscle- and fiber type-specific expression to reporter genes [28].
  • Conscious myo-/- mice evaluated by echocardiography display lowered cardiac output (0.64+/-0.06 vs. 0.75+/-0.09 ml x min(-1) x g(-1), myo-/- vs. WT, P<0.001), impaired systolic shortening (60+/-3.5 vs. 65+/-4%, myo-/- vs. WT, P<0.001) and fail to respond to beta1-stimulation [16].
  • We developed eight monoclonal antibodies to human cardiac Mb, characterized their epitopic reactivity, and determined which combinations of the antibodies are useful in two-site immunoassays [4].
  • We established two-site and three-site ELISA assays for Mb, by varying capture and tracer mAbs [29].

References

  1. Neuroglobin-overexpressing transgenic mice are resistant to cerebral and myocardial ischemia. Khan, A.A., Wang, Y., Sun, Y., Mao, X.O., Xie, L., Miles, E., Graboski, J., Chen, S., Ellerby, L.M., Jin, K., Greenberg, D.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Myoglobin protects the heart from inducible nitric-oxide synthase (iNOS)-mediated nitrosative stress. Gödecke, A., Molojavyi, A., Heger, J., Flögel, U., Ding, Z., Jacoby, C., Schrader, J. J. Biol. Chem. (2003) [Pubmed]
  3. Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice. Mammen, P.P., Kanatous, S.B., Yuhanna, I.S., Shaul, P.W., Garry, M.G., Balaban, R.S., Garry, D.J. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  4. Development and application of monoclonal antibodies to human cardiac myoglobin in a rapid fluorescence immunoassay. Silva, D.P., Landt, Y., Porter, S.E., Ladenson, J.H. Clin. Chem. (1991) [Pubmed]
  5. Recombinant expression of Mus musculus myoglobin. Bianchi, M., Clementi, M.E., Maras, B., Schininà, M.E., Bozzi, M., Giardina, B., Brancaccio, A. Protein Expr. Purif. (2003) [Pubmed]
  6. Mice without myoglobin. Garry, D.J., Ordway, G.A., Lorenz, J.N., Radford, N.B., Chin, E.R., Grange, R.W., Bassel-Duby, R., Williams, R.S. Nature (1998) [Pubmed]
  7. Presentation of antigen by mixed isotype class II molecules in normal H-2d mice. Ruberti, G., Sellins, K.S., Hill, C.M., Germain, R.N., Fathman, C.G., Livingstone, A. J. Exp. Med. (1992) [Pubmed]
  8. The T cell receptor repertoire influences V beta element usage in response to myoglobin. Ruberti, G., Gaur, A., Fathman, C.G., Livingstone, A.M. J. Exp. Med. (1991) [Pubmed]
  9. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. Romani, N., Koide, S., Crowley, M., Witmer-Pack, M., Livingstone, A.M., Fathman, C.G., Inaba, K., Steinman, R.M. J. Exp. Med. (1989) [Pubmed]
  10. Deciphering the mysteries of myoglobin in striated muscle. Conley, K.E., Ordway, G.A., Richardson, R.S. Acta Physiol. Scand. (2000) [Pubmed]
  11. The cytotoxic and genotoxic effects of conjugated trans-2-nonenal (T2N), an off-flavor compound in beer and heat processed food arising from lipid oxidation. Dey, E.S., Staniszewska, M., Paściak, M., Konopacka, M., Rogoliński, J., Gamian, A., Danielsson, B. Pol. J. Microbiol. (2005) [Pubmed]
  12. Inhibition of intracellular multiplication of human strains of Chlamydia trachomatis by nitric oxide. Igietseme, J.U., Uriri, I.M., Chow, M., Abe, E., Rank, R.G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  13. Role of myoglobin in the antioxidant defense of the heart. Flögel, U., Gödecke, A., Klotz, L.O., Schrader, J. FASEB J. (2004) [Pubmed]
  14. Changes in NO bioavailability regulate cardiac O2 consumption: control by intramitochondrial SOD2 and intracellular myoglobin. Li, W., Jue, T., Edwards, J., Wang, X., Hintze, T.H. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  15. The mouse myoglobin gene. Characterisation and sequence comparison with other mammalian myoglobin genes. Blanchetot, A., Price, M., Jeffreys, A.J. Eur. J. Biochem. (1986) [Pubmed]
  16. Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function. Merx, M.W., Gödecke, A., Flögel, U., Schrader, J. FASEB J. (2005) [Pubmed]
  17. Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart. Parsons, W.J., Richardson, J.A., Graves, K.H., Williams, R.S., Moreadith, R.W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  18. The myoglobin of rodents Proechimys guairae (casiragua) and Mus musculus (house mouse). Harris, D.E., Gurnett, A.M., Lehmann, H., Joysey, K.A. FEBS Lett. (1985) [Pubmed]
  19. Lack of myoglobin causes a switch in cardiac substrate selection. Flögel, U., Laussmann, T., Gödecke, A., Abanador, N., Schäfers, M., Fingas, C.D., Metzger, S., Levkau, B., Jacoby, C., Schrader, J. Circ. Res. (2005) [Pubmed]
  20. T cell clones reactive with sperm whale myoglobin. Isolation of clones with specificity for individual determinants on myoglobin. Infante, A.J., Atassi, M.Z., Fathman, C.G. J. Exp. Med. (1981) [Pubmed]
  21. Myoglobin: A scavenger of bioactive NO. Flögel, U., Merx, M.W., Godecke, A., Decking, U.K., Schrader, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  22. Renal uptake of myoglobin is mediated by the endocytic receptors megalin and cubilin. Gburek, J., Birn, H., Verroust, P.J., Goj, B., Jacobsen, C., Moestrup, S.K., Willnow, T.E., Christensen, E.I. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  23. Infection with Schistosoma mansoni alters Th1/Th2 cytokine responses to a non-parasite antigen. Kullberg, M.C., Pearce, E.J., Hieny, S.E., Sher, A., Berzofsky, J.A. J. Immunol. (1992) [Pubmed]
  24. Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers. Oh, M., Rybkin, I.I., Copeland, V., Czubryt, M.P., Shelton, J.M., van Rooij, E., Richardson, J.A., Hill, J.A., De Windt, L.J., Bassel-Duby, R., Olson, E.N., Rothermel, B.A. Mol. Cell. Biol. (2005) [Pubmed]
  25. Maximal oxygen consumption in relation to subordinate traits in lines of house mice selectively bred for high voluntary wheel running. Rezende, E.L., Gomes, F.R., Malisch, J.L., Chappell, M.A., Garland, T. J. Appl. Physiol. (2006) [Pubmed]
  26. Adaptation of the myoglobin knockout mouse to hypoxic stress. Schlieper, G., Kim, J.H., Molojavyi, A., Jacoby, C., Laussmann, T., Flögel, U., Gödecke, A., Schrader, J. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2004) [Pubmed]
  27. Source and component genes of a 6-200 Mb gene cluster in the house mouse. Weichenhan, D., Kunze, B., Winking, H., van Geel, M., Osoegawa, K., de Jong, P.J., Traut, W. Mamm. Genome (2001) [Pubmed]
  28. Regulatory elements governing transcription in specialized myofiber subtypes. Yan, Z., Serrano, A.L., Schiaffino, S., Bassel-Duby, R., Williams, R.S. J. Biol. Chem. (2001) [Pubmed]
  29. Synergistic effects in antigen capture ELISA using three monoclonal antibodies directed at different epitopes of the same antigen. Nikulina, V.A., Kizim, E.A., Massino, Y.S., Segal, O.L., Smirnova, M.B., Avilov, V.V., Saprigin, D.B., Smotrov, S.P., Tichtchenko, V.A., Kolyaskina, G.I., Dmitriev, A.D. Clin. Chim. Acta (2000) [Pubmed]
 
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