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Pucar D, Dzeja PP, Bast P, et al. Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy. Mol Cell Biochem. 2004;256(1):281-9doi: 10.1023/b:mcbi.0000009875.30308.7a.
Pucar, D., Dzeja, P. P., Bast, P., Gumina, R. J., Drahl, C., Lim, L., Juranic, N., Macura, S., & Terzic, A. (2004). Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy. Molecular and cellular biochemistry, 256(1), 281-9. https://doi.org/10.1023/b:mcbi.0000009875.30308.7a
Pucar, Darko, et al. "Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy." Molecular and cellular biochemistry vol. 256,1 (2004): 281-9. doi: https://doi.org/10.1023/b:mcbi.0000009875.30308.7a
Pucar D, Dzeja PP, Bast P, Gumina RJ, Drahl C, Lim L, Juranic N, Macura S, Terzic A. Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy. Mol Cell Biochem. 2004 Jan-Feb;256(1):281-9. doi: 10.1023/b:mcbi.0000009875.30308.7a. PMID: 14977188; PMCID: PMC2743901.
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Mol Cell Biochem. 2004 Jan-Feb;256(1):281-9. doi: 10.1023/b:mcbi.0000009875.30308.7a.

Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by 18O-assisted 31P NMR and 1H NMR spectroscopy.

Molecular and cellular biochemistry

Darko Pucar, Petras P Dzeja, Peter Bast, Richard J Gumina, Carmen Drahl, Lynette Lim, Nenad Juranic, Slobodan Macura, Andre Terzic

Affiliations

  1. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA.

PMID: 14977188 PMCID: PMC2743901 DOI: 10.1023/b:mcbi.0000009875.30308.7a

Abstract

Brief hypoxia or ischemia perturbs energy metabolism inducing paradoxically a stress-tolerant state, yet metabolic signals that trigger cytoprotection remain poorly understood. To evaluate bioenergetic rearrangements, control and hypoxic hearts were analyzed with 18O-assisted 31P NMR and 1H NMR spectroscopy. The 18O-induced isotope shift in the 31P NMR spectrum of CrP, betaADP and betaATP was used to quantify phosphotransfer fluxes through creatine kinase and adenylate kinase. This analysis was supplemented with determination of energetically relevant metabolites in the phosphomonoester (PME) region of 31P NMR spectra, and in both aromatic and aliphatic regions of 1H NMR spectra. In control conditions, creatine kinase was the major phosphotransfer pathway processing high-energy phosphoryls between sites of ATP consumption and ATP production. In hypoxia, creatine kinase flux was dramatically reduced with a compensatory increase in adenylate kinase flux, which supported heart energetics by regenerating and transferring beta- and gamma-phosphoryls of ATP. Activation of adenylate kinase led to a build-up of AMP, IMP and adenosine, molecules involved in cardioprotective signaling. 31P and 1H NMR spectral analysis further revealed NADH and H+ scavenging by alpha-glycerophosphate dehydrogenase (alphaGPDH) and lactate dehydrogenase contributing to maintained glycolysis under hypoxia. Hypoxia-induced accumulation of alpha-glycerophosphate and nucleoside 5'-monophosphates, through alphaGPDH and adenylate kinase reactions, respectively, was mapped within the increased PME signal in the 31P NMR spectrum. Thus, 18O-assisted 31P NMR combined with 1H NMR provide a powerful approach in capturing rearrangements in cardiac bioenergetics, and associated metabolic signaling that underlie the cardiac adaptive response to stress.

References

  1. FASEB J. 1998 May;12(7):523-9 - PubMed
  2. Mol Cell Biochem. 1998 Jul;184(1-2):169-82 - PubMed
  3. Mol Cell Biochem. 1998 Jul;184(1-2):231-47 - PubMed
  4. Am J Physiol. 1999 May;276(5 Pt 2):H1502-10 - PubMed
  5. Circ Res. 1999 May 28;84(10):1137-43 - PubMed
  6. Am J Physiol. 1998 Oct;275(4 Pt 1):E558-67 - PubMed
  7. Am J Cardiol. 1998 Sep 3;82(5A):54K-60K - PubMed
  8. Biochem Soc Symp. 1999;64:13-27 - PubMed
  9. Am J Physiol. 1999 Dec;277(6 Pt 2):H2167-75 - PubMed
  10. Biophys J. 2000 Jul;79(1):1-13 - PubMed
  11. Curr Cardiol Rep. 2000 May;2(3):212-7 - PubMed
  12. EMBO J. 2000 Dec 1;19(23):6371-81 - PubMed
  13. J Biol Chem. 2000 Dec 29;275(52):41424-9 - PubMed
  14. Ann Biomed Eng. 2000 Aug;28(8):871-6 - PubMed
  15. FASEB J. 2001 Jan;15(1):99-107 - PubMed
  16. Trends Cardiovasc Med. 2000 Aug;10(6):238-45 - PubMed
  17. J Mol Cell Cardiol. 2001 May;33(5):947-56 - PubMed
  18. Hum Mol Genet. 2001 May 15;10(11):1215-20 - PubMed
  19. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7623-8 - PubMed
  20. J Cardiovasc Magn Reson. 2000;2(1):23-32 - PubMed
  21. J Biol Chem. 2001 Nov 30;276(48):44812-9 - PubMed
  22. IUBMB Life. 2001 Sep-Nov;52(3-5):255-61 - PubMed
  23. J Clin Invest. 2002 Feb;109(4):509-16 - PubMed
  24. Am J Physiol Heart Circ Physiol. 2002 Aug;283(2):H776-82 - PubMed
  25. Cardiovasc Res. 2002 Aug 15;55(3):520-5 - PubMed
  26. Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13278-83 - PubMed
  27. J Mol Cell Cardiol. 2002 Sep;34(9):1077-89 - PubMed
  28. Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2106-13 - PubMed
  29. J Exp Biol. 2003 Jun;206(Pt 12):2039-47 - PubMed
  30. J Mol Cell Cardiol. 1970 Sep;1(3):325-39 - PubMed
  31. Circ Res. 1973 Jun;32(6):699-711 - PubMed
  32. Eur J Biochem. 1974 Oct 2;48(2):325-31 - PubMed
  33. Circ Res. 1975 Dec;37(6):742-51 - PubMed
  34. Curr Top Cell Regul. 1977;12:107-208 - PubMed
  35. Proc Natl Acad Sci U S A. 1978 Jan;75(1):200-3 - PubMed
  36. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3646-50 - PubMed
  37. J Biol Chem. 1985 Mar 25;260(6):3512-7 - PubMed
  38. Annu Rev Biochem. 1985;54:831-62 - PubMed
  39. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6142-5 - PubMed
  40. Circulation. 1986 Nov;74(5):1124-36 - PubMed
  41. Circ Res. 1988 Jul;63(1):1-15 - PubMed
  42. J Biol Chem. 1988 Aug 5;263(22):10600-7 - PubMed
  43. Biophys J. 1989 Jan;55(1):79-99 - PubMed
  44. Klin Wochenschr. 1989 May 2;67(9):465-76 - PubMed
  45. J Biol Chem. 1990 Jan 5;265(1):300-11 - PubMed
  46. Cardiovasc Res. 1990 Jun;24(6):510-20 - PubMed
  47. Basic Res Cardiol. 1990 Jul-Aug;85(4):342-57 - PubMed
  48. Annu Rev Med. 1991;42:225-46 - PubMed
  49. J Biol Chem. 1991 Aug 15;266(23):15110-9 - PubMed
  50. Biochem J. 1992 Jan 1;281 ( Pt 1):21-40 - PubMed
  51. Circulation. 1992 Jul;86(1):302-10 - PubMed
  52. Basic Res Cardiol. 1992 Nov-Dec;87(6):548-58 - PubMed
  53. Magn Reson Med. 1993 Mar;29(3):381-5 - PubMed
  54. Neuron. 1994 Apr;12(4):885-93 - PubMed
  55. Circulation. 1994 May;89(5):2283-9 - PubMed
  56. Mol Cell Biochem. 1994 Apr-May;133-134:125-44 - PubMed
  57. Mol Cell Biochem. 1994 Apr-May;133-134:155-92 - PubMed
  58. Am J Physiol. 1995 Mar;268(3 Pt 2):H935-44 - PubMed
  59. J Biol Chem. 1995 Mar 31;270(13):7311-9 - PubMed
  60. Am J Physiol. 1995 Sep;269(3 Pt 2):H1030-6 - PubMed
  61. Magn Reson Med. 1995 Sep;34(3):343-52 - PubMed
  62. NMR Biomed. 1995 May;8(3):118-26 - PubMed
  63. NMR Biomed. 1995 Aug;8(5):190-6 - PubMed
  64. J Biol Chem. 1996 May 31;271(22):12847-51 - PubMed
  65. Mol Cell Biochem. 1996 Jul-Aug;160-161:195-208 - PubMed
  66. Circulation. 1996 Dec 1;94(11):2831-6 - PubMed
  67. J Biol Chem. 1996 Dec 13;271(50):31903-8 - PubMed
  68. Biochim Biophys Acta. 1997 Jun 13;1320(2):208-16 - PubMed
  69. Int J Biochem Cell Biol. 1997 May;29(5):849-56 - PubMed
  70. Ann Thorac Surg. 1998 Feb;65(2):586-91 - PubMed

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