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Molecular Insights into the Functional Role of Myoglobin

  • Conference paper
Hypoxia and the Circulation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 618))

Abstract

Myoglobin is a cytoplasmic hemoprotein that is restricted to cardiomyocytes and oxidative skeletal muscle fibers. Myoglobin is a well-characterized protein and numerous studies have established that it has an essential role in facilitated oxygen transport in striated muscles. Recent strategies, using gene disruption technologies, have produced mice that lack myoglobin. These myoglobin deficient mice have a binary phenotype and a subpopulation of these mutant mice is viable and fertile. Characterization of the viable myoglobin null mice has uncovered a number of molecular and cellular adaptive mechanisms that function to promote oxygen delivery in the mutant striated muscle cell. Moreover, cellular and physiological studies, using the myoglobin deficient mouse model, support the conclusion that the functions of myoglobin include: facilitated oxygen transport, the storage of oxygen and a scavenger of nitric oxide or reactive oxygen species. Collectively, the use of genetic mouse models will further enhance our understanding of myoglobin function in normal and pathological muscle lineages.

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References

  1. Brunori M. Nitric oxide moves myoglobin centre stage. Trends Biochem Sci26: 209- 210, 2001.

    Article  CAS  PubMed  Google Scholar 

  2. Burmester T, Ebner B, Weich B, and Hankeln T. Cytoglobin: a novel globin type ubiquitously expressed in vertebrate tissues. Mol Biol Evol19: 416-421, 2002.

    CAS  PubMed  Google Scholar 

  3. Burmester T, Weich B, Reinhardt S, and Hankeln T. A vertebrate globin expressed in the brain. Nature407: 520-523, 2000.

    Article  CAS  PubMed  Google Scholar 

  4. Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, and Williams RS. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev12: 2499-2509, 1998.

    Article  CAS  PubMed  Google Scholar 

  5. Devlin BH, Wefald FC, Kraus WE, Bernard TS, and Williams RS. Identification of a muscle-specific enhancer within the 5’-flanking region of the human myoglobin gene. J Biol Chem264: 13896-13901, 1989.

    CAS  PubMed  Google Scholar 

  6. Dewilde S, Kiger L, Burmester T, Hankeln T, Baudin-Creuza V, Aerts T, Marden MC, Caubergs R, and Moens L. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J Biol Chem276: 38949-38955, 2001.

    Article  CAS  PubMed  Google Scholar 

  7. Flogel U, Godecke A, Klotz LO, and Schrader J. Role of myoglobin in the antioxidant defense of the heart. Faseb J18: 1156-1158, 2004.

    PubMed  Google Scholar 

  8. Flogel U, Merx MW, Godecke A, Decking UK, and Schrader J. Myoglobin: A scavenger of bioactive NO. Proc Natl Acad Sci U S A98: 735-740, 2001.

    Article  CAS  PubMed  Google Scholar 

  9. Fordel E, Geuens E, Dewilde S, Rottiers P, Carmeliet P, Grooten J, and Moens L. Cytoglobin expression is upregulated in all tissues upon hypoxia: an in vitro and in vivo study by quantitative real-time PCR. Biochem Biophys Res Commun319: 342- 348, 2004.

    Article  CAS  PubMed  Google Scholar 

  10. Fraser J, de Mello LV, Ward D, Rees HH, Williams DR, Fang Y, Brass A, Gracey AY, and Cossins AR. Hypoxia-inducible myoglobin expression in nonmuscle tissues. Proc Natl Acad Sci U S A103: 2977-2981, 2006.

    Article  CAS  PubMed  Google Scholar 

  11. Frauenfelder H and McMahon BH. Relaxations and fluctuations in myoglobin. Biosystems62: 3-8, 2001.

    Article  CAS  PubMed  Google Scholar 

  12. Frauenfelder H, McMahon BH, Austin RH, Chu K, and Groves JT. The role of structure, energy landscape, dynamics, and allostery in the enzymatic function of myoglobin. Proc Natl Acad Sci U S A98: 2370-2374, 2001.

    Article  CAS  PubMed  Google Scholar 

  13. Garry DJ, Bassel-Duby RS, Richardson JA, Grayson J, Neufer PD, and Williams RS. Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb. Dev Genet19: 146-156, 1996.

    Article  CAS  PubMed  Google Scholar 

  14. Garry DJ, Kanatous SB, and Mammen PP. Emerging roles for myoglobin in the heart. Trends Cardiovasc Med13: 111-116, 2003.

    Article  CAS  PubMed  Google Scholar 

  15. Garry DJ and Mammen PP. Neuroprotection and the role of neuroglobin. Lancet362: 342-343, 2003.

    Article  PubMed  Google Scholar 

  16. Garry DJ, Ordway GA, Lorenz JN, Radford NB, Chin ER, Grange RW, Bassel-Duby R, and Williams RS. Mice without myoglobin. Nature395: 905-908, 1998.

    Article  CAS  PubMed  Google Scholar 

  17. George P and Irvine DH. A possible structure for the higher oxidation state of metmyoglobin. Biochem J60: 596-604, 1955.

    CAS  PubMed  Google Scholar 

  18. Godecke A, Flogel U, Zanger K, Ding Z, Hirchenhain J, Decking UK, and Schrader J. Disruption of myoglobin in mice induces multiple compensatory mechanisms. Proc Natl Acad Sci U S A96: 10495-10500, 1999.

    Article  CAS  PubMed  Google Scholar 

  19. Godecke A, Molojavyi A, Heger J, Flogel U, Ding Z, Jacoby C, and Schrader J. Myoglobin protects the heart from inducible nitric-oxide synthase (iNOS)-mediated nitrosative stress. J Biol Chem278: 21761-21766, 2003.

    Article  PubMed  Google Scholar 

  20. Grange RW, Meeson A, Chin E, Lau KS, Stull JT, Shelton JM, Williams RS, and Garry DJ. Functional and molecular adaptations in skeletal muscle of myoglobinmutant mice. Am J Physiol Cell Physiol281: C1487-1494, 2001.

    CAS  PubMed  Google Scholar 

  21. Grayson J, Bassel-Duby R, and Williams RS. Collaborative interactions between MEF-2 and Sp1 in muscle-specific gene regulation. J Cell Biochem70: 366-375, 1998.

    Article  CAS  PubMed  Google Scholar 

  22. Kawai H, Nishino H, Nishida Y, Masuda K, and Saito S. Localization of myoglobin in human muscle cells by immunoelectron microscopy. Muscle Nerve10: 144-149, 1987.

    Article  CAS  PubMed  Google Scholar 

  23. Kendrew JC. Myoglobin and the structure of proteins. Science139: 1259-1266, 1963.

    Article  CAS  PubMed  Google Scholar 

  24. Kendrew JC, Bodo G, Dintzis HM, Parrish RG, Wyckoff H, and Phillips DC. A threedimensional model of the myoglobin molecule obtained by x-ray analysis. Nature 181: 662-666, 1958.

    Article  CAS  PubMed  Google Scholar 

  25. Mammen PP, Kanatous SB, Yuhanna IS, Shaul PW, Garry MG, Balaban RS, and Garry DJ. Hypoxia-Induced Left Ventricular Dysfunction in Myoglobin Deficient Mice. Am J Physiol Heart Circ Physiol, 2003.

    Google Scholar 

  26. Mammen PP, Shelton JM, Goetsch SC, Williams SC, Richardson JA, Garry MG, and Garry DJ. Neuroglobin, a novel member of the globin family, is expressed in focal regions of the brain. J Histochem Cytochem50: 1591-1598, 2002.

    CAS  PubMed  Google Scholar 

  27. Mammen PP, Shelton JM, Ye Q, Kanatous SB, McGrath AJ, Richardson JA, and Garry DJ. Cytoglobin is a stress-responsive hemoprotein expressed in the developing and adult brain. J Histochem Cytochem54: 1349-1361, 2006.

    Article  CAS  PubMed  Google Scholar 

  28. Meeson AP, Radford N, Shelton JM, Mammen PP, DiMaio JM, Hutcheson K, Kong Y, Elterman J, Williams RS, and Garry DJ. Adaptive mechanisms that preserve cardiac function in mice without myoglobin. Circ Res88: 713-720, 2001.

    Article  CAS  PubMed  Google Scholar 

  29. Millikan GA. Experiments on muscle haemoglobin in vivo, the instantaneous measurement of muscle metabolism. Pro Roy SocB123, 218, 1937.

    Article  Google Scholar 

  30. Mitsui T, Kawai H, Naruo T, and Saito S. Ultrastructural localization of myoglobin mRNA in human skeletal muscle. Histochemistry101: 99-104, 1994.

    Article  CAS  PubMed  Google Scholar 

  31. Noren SR, Williams TM, Pabst DA, McLellan WA, and Dearolf JL. The development of diving in marine endotherms: preparing the skeletal muscles of dolphins, penguins, and seals for activity during submergence. J Comp Physiol [B]171: 127- 134, 2001.

    CAS  Google Scholar 

  32. Ordway GA and Garry DJ. Myoglobin: an essential hemoprotein in striated muscle. J Exp Biol207: 3441-3446, 2004.

    Article  CAS  PubMed  Google Scholar 

  33. Parsons WJ, Richardson JA, Graves KH, Williams RS, and Moreadith RW. Gradients of transgene expression directed by the human myoglobin promoter in the developing mouse heart. Proc Natl Acad Sci U S A90: 1726-1730, 1993.

    Article  CAS  PubMed  Google Scholar 

  34. Perkoff GT and Tyler FH. Estimation and physical properties of myoglobin in various species. Metabolism7: 751-759, 1958.

    CAS  PubMed  Google Scholar 

  35. Schmidt M, Gerlach F, Avivi A, Laufs T, Wystub S, Simpson JC, Nevo E, Saaler- Reinhardt S, Reuss S, Hankeln T, and Burmester T. Cytoglobin is a respiratory protein in connective tissue and neurons, which is up-regulated by hypoxia. J Biol Chem279: 8063-8069, 2004.

    Article  CAS  PubMed  Google Scholar 

  36. Sun Y, Jin K, Mao XO, Zhu Y, and Greenberg DA. Neuroglobin is up-regulated by and protects neurons from hypoxic-ischemic injury. Proc Natl Acad Sci U S A98: 15306- 15311, 2001.

    Article  CAS  PubMed  Google Scholar 

  37. Swaanenburg JC, Visser-VanBrummen PJ, DeJongste MJ, and Tiebosch AT. The content and distribution of troponin I, troponin T, myoglobin, and alphahydroxybutyric acid dehydrogenase in the human heart. Am J Clin Pathol115: 770- 777, 2001.

    Article  CAS  PubMed  Google Scholar 

  38. Trent JT, 3rd and Hargrove MS. A ubiquitously expressed human hexacoordinate hemoglobin. J Biol Chem277: 19538-19545, 2002.

    Article  CAS  PubMed  Google Scholar 

  39. Wegener JW, Godecke A, Schrader J, and Nawrath H. Effects of nitric oxide donors on cardiac contractility in wild-type and myoglobin-deficient mice. Br J Pharmacol 136: 415-420, 2002.

    Article  CAS  PubMed  Google Scholar 

  40. Weller PA, Price M, Isenberg H, Edwards YH, and Jeffreys AJ. Myoglobin expression: early induction and subsequent modulation of myoglobin and myoglobin mRNA during myogenesis. Mol Cell Biol6: 4539-4547, 1986.

    CAS  PubMed  Google Scholar 

  41. Wittenberg JB. The molecular mechanism of hemoglobin-facilitated oxygen diffusion. J Biol Chem241: 104-114, 1966.

    CAS  PubMed  Google Scholar 

  42. Wittenberg JB. Myoglobin-facilitated oxygen diffusion: role of myoglobin in oxygen entry into muscle. Physiol Rev50: 559-636, 1970.

    CAS  PubMed  Google Scholar 

  43. Wittenberg JB and Wittenberg BA. Myoglobin function reassessed. J Exp Biol206: 2011-2020, 2003.

    Article  CAS  PubMed  Google Scholar 

  44. Wunderlich C, Flogel U, Godecke A, Heger J, and Schrader J. Acute inhibition of myoglobin impairs contractility and energy state of iNOS-overexpressing hearts. Circ Res92: 1352-1358, 2003.

    Article  CAS  PubMed  Google Scholar 

  45. Yan Z, Serrano AL, Schiaffino S, Bassel-Duby R, and Williams RS. Regulatory elements governing transcription in specialized myofiber subtypes. J Biol Chem276: 17361-17366, 2001.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Daniel J. Garry & Pradeep P. A. Mammen

  2. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Daniel J. Garry

  3. Donald W. Reynolds Cardiovascular Clinical Research Center at UT Southwestern Medical Center, Dallas, Texas, USA

    Daniel J. Garry & Pradeep P. A. Mammen

Authors
  1. Daniel J. Garry
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Editors and Affiliations

  1. Altitude Research Center, University of Colorado, Health Sciences Center, Mail Stop F524, PO Box 6508, Aurora, Colorado, 80045-0508, USA

    Robert C. Roach Ph.D. (Research Director) (Research Director)

  2. UCSD Dept Medicine, 0623, 9500 Gilman Avenue, La Jolla, CA, 92093-0623, USA

    Peter D. Wagner

  3. Institute for Altitude Medicine, Telluride Medical Center, 500 W. Pacific, Telluride, Colorado, 81435, USA

    Peter H. Hackett

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© 2007 Springer Science+Business Media, LLC

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Garry, D.J., Mammen, P.P.A. (2007). Molecular Insights into the Functional Role of Myoglobin. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia and the Circulation. Advances in Experimental Medicine and Biology, vol 618. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-75434-5_14

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