Publications

  1. Dutta, D., and Fliegel, L. (2018) Structure and function of yeast and fungal Na(+) /H(+) antiporters. IUBMB Life 70, 23-31.

  2. Amith, S. R., and Fliegel, L. (2017) Na(+)/H(+) exchanger-mediated hydrogen ion extrusion as a carcinogenic signal in triple-negative breast cancer etiopathogenesis and prospects for its inhibition in therapeutics. Semin Cancer Biol 43, 35-41.

  3. Amith, S. R., Vincent, K. M., Wilkinson, J. M., Postovit, L. M., and Fliegel, L. (2017) Defining the Na(+)/H(+) exchanger NHE1 interactome in triple-negative breast cancer cells. Cell Signal 29, 69-77.

  4. Dutta, D., Shin, K., Rainey, J. K., and Fliegel, L. (2017) Transmembrane Segment XI of the Na(+)/H(+) Antiporter of S. pombe is a Critical Part of the Ion Translocation Pore. Sci Rep 7, 12793.

  5. Fliegel, L. (2017) beta-Raf activation of the myocardial Na(+)/H(+) exchanger. Channels (Austin) 11, 181-182.

  6. Odunewu-Aderibigbe, A., and Fliegel, L. (2017) Heat shock proteins and the Na(+)/H(+) exchanger. Channels (Austin) 11, 380-382.

  7. Odunewu-Aderibigbe, A., and Fliegel, L. (2017) Protein mediated regulation of the NHE1 isoform of the Na(+)/H(+) exchanger in renal cells. A regulatory role of Hsp90 and AKT kinase. Cell Signal 36, 145-153.

  8. Amith, S. R., Wilkinson, J. M., and Fliegel, L. (2016) KR-33028, a potent inhibitor of the Na(+)/H(+) exchanger NHE1, suppresses metastatic potential of triple-negative breast cancer cells. Biochem Pharmacol 118, 31-39.

  9. Li, X., Augustine, A., Chen, S., and Fliegel, L. (2016) Stop Codon Polymorphisms in the Human SLC9A1 Gene Disrupt or Compromise Na+/H+ Exchanger Function. PLoS One 11, e0162902.

  10. Li, X., Augustine, A., Sun, D., Li, L., and Fliegel, L. (2016) Activation of the Na(+)/H(+) exchanger in isolated cardiomyocytes through beta-Raf dependent pathways. Role of Thr(653) of the cytosolic tail. J Mol Cell Cardiol 99, 65-75.

  11.  Amith, S. R., and Fliegel, L. (2016) The Na+/H+ exchanger in metastasis. Aging (Albany NY) 8, 1291. 27434610. 10.18632/aging.101002

  12.  Amith, S. R., Wilkinson, J. M., and Fliegel, L. (2016) Na+/H+ exchanger NHE1 regulation modulates metastatic potential and epithelial-mesenchymal transition of triple-negative breast cancer cells. Oncotarget 7, 21091-21113. 27049728. 10.18632/oncotarget.8520

  13.  Ullah, A., Dutta, D., and Fliegel, L. (2016) Expression and characterization of the SOS1 Arabidopsis salt tolerance protein. Mol Cell Biochem 415, 133-143. 26992907. 10.1007/s11010-016-2685-2

  14. Y. Liu, A. Basu, Xiuju Li and L. Fliegel.  Topological Analysis of the Na+/H+ Exchanger. BBA Biomembranes 1848(10PtA):2385-93.  DOI 10.1016/j.bbamem.2015.07.011. 26215741

  15. S.C. Guffey, L. Fliegel, G.G. Goss. (2015) Cloning and characterization of shark gill Na+/H+Exchanger isoforms NHE2 and NHE3 from the Pacific dogfish Squalus suckleyi Comparative Biochemistry and Physiology - Part B: Biochemistry & Molecular Biology 188:46-53. DOI10.1016/j.cbpb.2015.06.003. 26112825

  16. Amith, R.S, S. Fong, S. Baksh and L. Fliegel.  Na+/H+ Exchange in the Tumour Microenvironment: Does NHE1 Drive Breast Cancer Carcinogenesis?  International Journal of Developmental Biology.  59:367-377. 26679950 

  17. Iman A. Mohamed, Alain-Pierre Gadeau, Gary Lopaschuk, Larry Fliegel, Mohamed Mlih, Nabeel Abdulrahman, Natasha Fillmore, Fatima Mraiche. Na+/H+ Exchanger Isoform 1-Induced Osteopontin Expression Facilitates Cardiomyocyte Hypertrophy Through p90 Ribosomal S6 Kinase. (2015) PLOS One 10(4) e0123318. DOI 10.1371/journal.pone. 0123318. 25884410

  18. Li, X. and Fliegel, L. (2015) A Novel Human Mutation in the SLC9A1 Gene Results in Abolition of Na+/H+ Exchanger Activity. Plos One 10(3) e0119453 DOI 10.1371/journal.pone.0119453. 25760855

  19. Schammim Ray Amith, Jodi Marie Wilkinson, S. Baksh and Larry Fliegel (2015) The Na+/H+exchanger (NHE1) as a novel co-adjuvant target in paclitaxel therapy of triple-negative breast cancer cells. Oncotarget 6(2):1262-75. 25514463.

  20. Guissart, C., Li, X., Leheup, B., Drouot, N., Montaut-Verient, B., Raffo, E., Jonveaux, P., Roux, A. F., Claustres, M., Fliegel, L., and Koenig, M. (2015) Mutation of SLC9A1, encoding the major Na+/H+ exchanger, causes ataxia-deafness Lichtenstein-Knorr syndrome. Hum Mol Genet 24, 463-470. 25205112.

  21. Odunewu-Aderibigbe, A., and Fliegel, L. (2014) The Na(+) /H(+) exchanger and pH regulation in the heart. IUBMB Life 66, 679-685. 25354428.

  22. Li, X., Ma, Y., and Fliegel, L. (2014) Functional role of arginine 425 in the mammalian Na(+)/H(+) exchanger. Biochem Cell Biol 92, 541-546. 25350536.

  23. Alves, C., Ma, Y., Li, X. and Fliegel, L. (2014) Characterization of human mutations in phosphorylatable
    amino acids of the cytosolic regulatory tail of SLC9A1. Biochem. Cell Biol. 92: 1–6. 25162926

  24. Alves, C., Lee, B. L., Sykes, B. D., and Fliegel, L. (2014) Structural and Functional Analysis of the Transmembrane Segment Pair VI and VII of the NHE1 Isoform of the Na(+)/H(+) Exchanger. Biochemistry 53, 3658-3670. 24840010

  25. Kemp, G., Fliegel, L., and Young, H. S. (2014) Membrane transport piece by piece: production of transmembrane peptides for structural and functional studies. Curr Protoc Protein Sci 75, Unit 29 28. 24510677

  26. Ullah, A., El-Magd, R. A., and Fliegel, L. (2014) Functional role and analysis of cysteine residues of the salt tolerance protein Sod2. Mol Cell Biochem 386, 85-98. 24104454

  27. Li, X., Prins, D., Michalak, M., and Fliegel, L. (2013) Calmodulin-dependent binding to the NHE1 cytosolic tail mediates activation of the Na+/H+ exchanger by Ca2+ and endothelin. Am J Physiol Cell Physiol 305, C1161-1169. 24088894

  28. Ullah, A., Kemp, G., Lee, B., Alves, C., Young, H., Sykes, B. D., and Fliegel, L. (2013) Structural and functional analysis of transmembrane segment IV of the salt tolerance protein Sod2. J Biol Chem 288, 24609-24624. 23836910

  29. Odunewu, A., and Fliegel, L. (2013) Acidosis-mediated regulation of the NHE1 isoform of the Na(+)/H(+) exchanger in renal cells. Am J Physiol Renal Physiol 305, F370-381. 23678047

  30. Li, X., Khan, M. F., Schriemer, D. C., and Fliegel, L. (2013) Structural changes in the C-terminal regulatory region of the Na(+)/H(+) exchanger mediate phosphorylation induced regulation. J Mol Cell Cardiol 61, 153-163. 23602949

  31. Amith, S. R., and Fliegel, L. (2013) Regulation of the Na+/H+ Exchanger (NHE1) in Breast Cancer Metastasis. Cancer Res 73, 1259-1264. 23393197

  32. Lee, B. L., Sykes, B. D., and Fliegel, L. (2013) Structural and functional insights into the cardiac Na(+)/H(+) exchanger. J Mol Cell Cardiol 61, 60-67. 23220151

  33. Lee, B. L., Liu, Y., Li, X., Sykes, B. D., and Fliegel, L. (2012) Structural and functional analysis of extracellular loop 4 of the Nhe1 isoform of the Na(+)/H(+) exchanger. Biochim Biophys Acta 1818, 2783-2790. 22772156

  34. Blough, M. D., Al-Najjar, M., Chesnelong, C., Binding, C. E., Rogers, A. D., Luchman, H. A., Kelly, J. J., Fliegel, L., Morozova, O., Yip, S., Marra, M., Weiss, S., Chan, J. A., and Cairncross, J. G. (2012) DNA hypermethylation and 1p Loss silence NHE-1 in oligodendroglioma. Ann Neurol 71, 845-849. 22718548

  35. Vanier, H. V., Mraiche, F., Li, X., and Fliegel, L. (2012) Gender-specific effects of exercise on cardiac pathology in Na(+)/H(+) exchanger overexpressing mice. Mol Cell Biochem 368, 103-110. 22627677

  36. Fliegel, L. (2012) Na+/H+ Exchangers, Structure, and Function: Role in Human Health and Disease. in V.N. Uversky, R.H. Kretsinger, E.A. Permyakov (eds.), Encyclopedia of Metalloproteins, DOI 10.1007/978-1-4614-1533-6, Springer Science+Business Media, LLC

  37. Mraiche, F., and Fliegel, L. (2011) Elevated expression of activated Na(+)/H(+) exchanger protein induces hypertrophy in isolated rat neonatal ventricular cardiomyocytes. Mol Cell Biochem 358, 179-187. 21720766

  38. Tzeng, J., Lee, B. L., Sykes, B. D., and Fliegel, L. (2011) Structural and functional analysis of critical amino acids in TMVI of the NHE1 isoform of the Na+/H+ exchanger. Biochim Biophys Acta 1808, 2327-2335. 21600870

  39. Lee, B. L., Sykes, B. D., and Fliegel, L. (2011) Structural analysis of the Na+/H+ exchanger isoform 1 (NHE1) using the divide and conquer approach. Biochem Cell Biol 89, 189-199. 21455270

  40. Alexander, R. T., and Fliegel, L. (2011) Report on the Na+/H+ Exchanger Satellite Meeting at the 53rd Annual Meeting of the Canadian Society of Biochemistry, Molecular and Cellular Biology. Biochem Cell Biol 89, 85-86. 21455260

  41. Mraiche, F., Oka, T., Gan, X. T., Karmazyn, M., and Fliegel, L. (2011) Activated NHE1 is required to induce early cardiac hypertrophy in mice. Basic Res Cardiol 106, 603-616. 21359875

  42. Karki, P., Li, X., Schrama, D., and Fliegel, L. (2011) B-Raf associates with and activates the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 286, 13096-13105. 21345796

  43. Fliegel, L.(2011) Elevated Na+/H+ exchanger expression and its role in myocardial disease. in N.S. Dhalla, M. Nagano, B. Ostadal (eds.), Molecular Defects in Cardiovascular Disease, 43DOI 10.1007/978-1-4419-7130-2_4, Springer Science+Business Media, LLC

  44. Sarigianni, M., Tsapas, A., Mikhailidis, D. P., Kaloyianni, M., Koliakos, G., Fliegel, L., and Paletas, K. (2010) Na+ H+ exchanger-1: a link with atherogenesis? Expert Opin Investig Drugs 19, 1545-1556. 21047280

  45. Mraiche, F., Wagg, C. S., Lopaschuk, G. D., and Fliegel, L. (2011) Elevated levels of activated NHE1 protect the myocardium and improve metabolism following ischemia/reperfusion injury. J Mol Cell Cardiol 50, 157-164. 20974148

  46. Tzeng, J., Lee, B. L., Sykes, B. D., and Fliegel, L. (2010) Structural and functional analysis of transmembrane segment VI of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 285, 36656-36665. 20843797

  47. Karki, P., Coccaro, E., and Fliegel, L. (2010) Sustained intracellular acidosis activates the myocardial Na(+)/H(+) exchanger independent of amino acid Ser(703) and p90(rsk). Biochim Biophys Acta 1798, 1565-1576. 20471361

  48. Xue, J., Mraiche, F., Zhou, D., Karmazyn, M., Oka, T., Fliegel, L., and Haddad, G. G. (2010) Elevated myocardial Na+/H+ exchanger isoform 1 activity elicits gene expression that leads to cardiac hypertrophy. Physiol Genomics 42, 374-383. 20460605

  49. Karki, P., and Fliegel, L. (2010) Overexpression of the NHE1 isoform of the Na(+)/H (+) exchanger causes elevated apoptosis in isolated cardiomyocytes after hypoxia/reoxygenation challenge. Mol Cell Biochem 338, 47-57. 19949839

  50. Lee, B. L., Li, X., Liu, Y., Sykes, B. D., and Fliegel, L. (2009) Structural and functional analysis of extracellular loop 2 of the Na(+)/H(+) exchanger. Biochim Biophys Acta 1788, 2481-2488. 19835836

  51. Reddy, T., Li, X., Fliegel, L., Sykes, B. D., and Rainey, J. K. (2010) Correlating structure, dynamics, and function in transmembrane segment VII of the Na+/H+ exchanger isoform 1. Biochim Biophys Acta 1798, 94-104. 19595986

  52. Coccaro, E., Karki, P., Cojocaru, C., and Fliegel, L. (2009) Phenylephrine and sustained acidosis activate the neonatal rat cardiomyocyte Na+/H+ exchanger through phosphorylation of amino acids Ser770 and Ser771. Am J Physiol Heart Circ Physiol 297, H846-858. 19542484

  53. Lee, B. L., Li, X., Liu, Y., Sykes, B. D., and Fliegel, L. (2009) Structural and functional analysis of transmembrane XI of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 284, 11546-11556. 19176522

  54. Ndayizeye, M., Touret, N., and Fliegel, L. (2009) Proline 146 is critical to the structure, function and targeting of sod2, the Na+/H+ exchanger of Schizosaccharomyces pombe. Biochim Biophys Acta 1788, 983-992. 19171118

  55. Baczko, I., Mraiche, F., Light, P. E., and Fliegel, L. (2008) Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing elevated levels of the Na+/H+ exchanger. Can J Physiol Pharmacol 86, 850-859. 19088806

  56. Fliegel, L. (2009) Regulation of the Na(+)/H(+) exchanger in the healthy and diseased myocardium. Expert Opin Ther Targets 13, 55-68. 19063706

  57. Li, X., Karki, P., Lei, L., Wang, H., and Fliegel, L. (2009) Na+/H+ exchanger isoform 1 facilitates cardiomyocyte embryonic stem cell differentiation. Am J Physiol Heart Circ Physiol 296, H159-170. 19011045

  58. Kemp, G., Young, H., and Fliegel, L. (2008) Structure and function of the human Na+/H+ exchanger isoform 1. Channels (Austin) 2, 329-336. 19001864

  59. Grenier, A. L., Abu-ihweij, K., Zhang, G., Ruppert, S. M., Boohaker, R., Slepkov, E. R., Pridemore, K., Ren, J. J., Fliegel, L., and Khaled, A. R. (2008) Apoptosis-induced alkalinization by the Na+/H+ exchanger isoform 1 is mediated through phosphorylation of amino acids Ser726 and Ser729. Am J Physiol Cell Physiol 295, C883-896. 18701649

  60. Chen, H., and Fliegel, L. (2008) Expression, purification, and reconstitution of the Na(+)/H (+) exchanger sod2 in Saccharomyces cerevisiae. Mol Cell Biochem 319, 79-86. 18629612

  61. Reddy, T., Ding, J., Li, X., Sykes, B. D., Rainey, J. K., and Fliegel, L. (2008) Structural and functional characterization of transmembrane segment IX of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 283, 22018-22030. 18508767

  62. Fliegel, L. (2008) Molecular biology of the myocardial Na+/H+ exchanger. J Mol Cell Cardiol 44, 228-237. 18191941

  63. Moncoq, K., Kemp, G., Li, X., Fliegel, L., and Young, H. S. (2008) Dimeric structure of human Na+/H+ exchanger isoform 1 overproduced in Saccharomyces cerevisiae. J Biol Chem 283, 4145-4154. 18077454

  64. Slepkov, E., Ding, J., Han, J., and Fliegel, L. (2007) Mutational analysis of potential pore-lining amino acids in TM IV of the Na(+)/H(+) exchanger. Biochim Biophys Acta 1768, 2882-2889. 17935692

  65. Ding, J., Ng, R. W., and Fliegel, L. (2007) Functional characterization of the transmembrane segment VII of the NHE1 isoform of the Na+/H+ exchanger. Can J Physiol Pharmacol 85, 319-325. 17612640

  66. Kumar, A. P., Chang, M. K., Fliegel, L., Pervaiz, S., and Clement, M. V. (2007) Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death Differ 14, 1733-1746. 17571084

  67. Coccaro, E., Mraiche, F., Malo, M., Vandertol-Vanier, H., Bullis, B., Robertson, M., and Fliegel, L. (2007) Expression and characterization of the Na+/H+ exchanger in the mammalian myocardium. Mol Cell Biochem 302, 145-155. 17431747

  68. Malo, M. E., and Fliegel, L. (2006) Physiological role and regulation of the Na+/H+ exchanger. Can J Physiol Pharmacol 84, 1081-1095. 17218973

  69. Rainey, J. K., Fliegel, L., and Sykes, B. D. (2006) Strategies for dealing with conformational sampling in structural calculations of flexible or kinked transmembrane peptides. Biochem Cell Biol 84, 918-929. 17215879

  70. Slepkov, E. R., Rainey, J. K., Sykes, B. D., and Fliegel, L. (2007) Structural and functional analysis of the Na+/H+ exchanger. Biochem J 401, 623-633. 17209804

  71. Malo, M. E., Li, L., and Fliegel, L. (2007) Mitogen-activated protein kinase-dependent activation of the Na+/H+ exchanger is mediated through phosphorylation of amino acids Ser770 and Ser771. J Biol Chem 282, 6292-6299. 17209041

  72. Imahashi, K., Mraiche, F., Steenbergen, C., Murphy, E., and Fliegel, L. (2007) Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the myocardium. Am J Physiol Heart Circ Physiol 292, H2237-2247. 17209001

  73. Ding, J., Rainey, J. K., Xu, C., Sykes, B. D., and Fliegel, L. (2006) Structural and functional characterization of transmembrane segment VII of the Na+/H+ exchanger isoform 1. J Biol Chem 281, 29817-29829. 16861220

  74. Li, X., Liu, Y., Alvarez, B. V., Casey, J. R., and Fliegel, L. (2006) A novel carbonic anhydrase II binding site regulates NHE1 activity. Biochemistry 45, 2414-2424. 16475831

  75. Akram, S., Teong, H. F., Fliegel, L., Pervaiz, S., and Clement, M. V. (2006) Reactive oxygen species-mediated regulation of the Na+-H+ exchanger 1 gene expression connects intracellular redox status with cells' sensitivity to death triggers. Cell Death Differ 13, 628-641. 16179939

  76. Karmazyn, M., Sawyer, M., and Fliegel, L. (2005) The Na(+)/H(+) exchanger: a target for cardiac therapeutic intervention. Curr Drug Targets Cardiovasc Haematol Disord 5, 323-335. 16101565

  77. Fliegel, L., Wiebe, C., Chua, G., and Young, P. G. (2005) Functional expression and cellular localization of the Na+/H+ exchanger Sod2 of the fission yeast Schizosaccharomyces pombe. Can J Physiol Pharmacol 83, 565-572. 16091782

  78. Misik, A. J., Perreault, K., Holmes, C. F., and Fliegel, L. (2005) Protein phosphatase regulation of Na+/H+ exchanger isoform I. Biochemistry 44, 5842-5852. 15823043

  79. Stupak, J., Liu, H., Wang, Z., Brix, B. J., Fliegel, L., and Li, L. (2005) Nanoliter sample handling combined with microspot MALDI-MS for detection of gel-separated phosphoproteins. J Proteome Res 4, 515-522. 15822929

  80. Fliegel, L. (2005) Identification of conserved polar residues important for salt tolerance by the Na+/H+ exchanger of Schizosaccharomyces pombe. Mol Cell Biochem 268, 83-92. 15724441

  81. Slepkov, E. R., Rainey, J. K., Li, X., Liu, Y., Cheng, F. J., Lindhout, D. A., Sykes, B. D., and Fliegel, L. (2005) Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem 280, 17863-17872. 15677483

  82. Fliegel, L., and Karmazyn, M. (2004) The cardiac Na-H exchanger: a key downstream mediator for the cellular hypertrophic effects of paracrine, autocrine and hormonal factors. Biochem Cell Biol 82, 626-635. 15674430

  83. Li, X., Ding, J., Liu, Y., Brix, B. J., and Fliegel, L. (2004) Functional analysis of acidic amino acids in the cytosolic tail of the Na+/H+ exchanger. Biochemistry 43, 16477-16486. 15610042

  84. Fliegel, L. (2005) The Na+/H+ exchanger isoform 1. Int J Biochem Cell Biol 37, 33-37. 15381146

  85. Liu, H., Stupak, J., Zheng, J., Keller, B. O., Brix, B. J., Fliegel, L., and Li, L. (2004) Open tubular immobilized metal ion affinity chromatography combined with MALDI MS and MS/MS for identification of protein phosphorylation sites. Anal Chem 76, 4223-4232. 15253667

  86. Slepkov, E., and Fliegel, L. (2004) Regulation of expression of the Na+/H+ exchanger by thyroid hormone. Vitam Horm 69, 249-269. 15196885

  87. Slepkov, E. R., Chow, S., Lemieux, M. J., and Fliegel, L. (2004) Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1. Biochem J 379, 31-38. 14680478

  88. Wiebe, C. A., Rieder, C., Young, P. G., Dibrov, P., and Fliegel, L. (2003) Functional analysis of amino acids of the Na+/H+ exchanger that are important for proton translocation. Mol Cell Biochem 254, 117-124. 14674689

  89. Karmazyn, M., Liu, Q., Gan, X. T., Brix, B. J., and Fliegel, L. (2003) Aldosterone increases NHE-1 expression and induces NHE-1-dependent hypertrophy in neonatal rat ventricular myocytes. Hypertension 42, 1171-1176. 14610099

  90. Li, X., Liu, Y., Kay, C. M., Muller-Esterl, W., and Fliegel, L. (2003) The Na+/H+ exchanger cytoplasmic tail: structure, function, and interactions with tescalcin. Biochemistry 42, 7448-7456. 12809501

  91. Rieder, C. V., and Fliegel, L. (2003) Transcriptional regulation of Na+/H+ exchanger expression in the intact mouse. Mol Cell Biochem 243, 87-95. 12619893

  92. Fliegel, L., Wiebe, C., Murtazina, R., Dibrov, P., Booth, B. J., Bullis, B. L., DiBattista, E., and Singh, D. N. (2002) Functional analysis of polar residues important for activity of Na+/H+ exchangers. Ann N Y Acad Sci 976, 117-120. 12502549

  93. Slepkov, E., and Fliegel, L. (2002) Structure and function of the NHE1 isoform of the Na+/H+ exchanger. Biochem Cell Biol 80, 499-508. 12440691

  94. Bullis, B. L., Li, X., Singh, D. N., Berthiaume, L. G., and Fliegel, L. (2002) Properties of the Na+/H+ exchanger protein. Detergent-resistant aggregation and membrane microdistribution. Eur J Biochem 269, 4887-4895. 12354120

  95. Li, X., Alvarez, B., Casey, J. R., Reithmeier, R. A., and Fliegel, L. (2002) Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger. J Biol Chem 277, 36085-36091. 12138085

  96. Rothstein, E. C., Byron, K. L., Reed, R. E., Fliegel, L., and Lucchesi, P. A. (2002) H(2)O(2)-induced Ca(2+) overload in NRVM involves ERK1/2 MAP kinases: role for an NHE-1-dependent pathway. Am J Physiol Heart Circ Physiol 283, H598-605. 12124207

  97. Rieder, C. V., and Fliegel, L. (2002) Developmental regulation of Na(+)/H(+) exchanger expression in fetal and neonatal mice. Am J Physiol Heart Circ Physiol 283, H273-283. 12063300

  98. Li, X., Misik, A. J., Rieder, C. V., Solaro, R. J., Lowen, A., and Fliegel, L. (2002) Thyroid hormone receptor alpha 1 regulates expression of the Na+/H+ exchanger (NHE1). J Biol Chem 277, 28656-28662. 12039959

  99. Khaled, A. R., Moor, A. N., Li, A., Kim, K., Ferris, D. K., Muegge, K., Fisher, R. J., Fliegel, L., and Durum, S. K. (2001) Trophic factor withdrawal: p38 mitogen-activated protein kinase activates NHE1, which induces intracellular alkalinization. Mol Cell Biol 21, 7545-7557. 11604491

  100. Wei, S., Rothstein, E. C., Fliegel, L., Dell'Italia, L. J., and Lucchesi, P. A. (2001) Differential MAP kinase activation and Na(+)/H(+) exchanger phosphorylation by H(2)O(2) in rat cardiac myocytes. Am J Physiol Cell Physiol 281, C1542-1550. 11600417

  101. Murtazina, R., Booth, B. J., Bullis, B. L., Singh, D. N., and Fliegel, L. (2001) Functional analysis of polar amino-acid residues in membrane associated regions of the NHE1 isoform of the mammalian Na+/H+ exchanger. Eur J Biochem 268, 4674-4685. 11532004

  102. Fliegel, L. (2001) Regulation of myocardial Na+/H+ exchanger activity. Basic Res Cardiol 96, 301-305. 11518184

  103. Wiebe, C. A., Dibattista, E. R., and Fliegel, L. (2001) Functional role of polar amino acid residues in Na+/H+ exchangers. Biochem J 357, 1-10. 11415429

  104. Moor, A. N., Gan, X. T., Karmazyn, M., and Fliegel, L. (2001) Activation of Na+/H+ exchanger-directed protein kinases in the ischemic and ischemic-reperfused rat myocardium. J Biol Chem 276, 16113-16122. 11279085

  105. Fernandez-Rachubinski, F., and Fliegel, L. (2001) COUP-TFI and COUP-TFII regulate expression of the NHE through a nuclear hormone responsive element with enhancer activity. Eur J Biochem 268, 620-634. 11168401

  106. Guo, L., Lynch, J., Nakamura, K., Fliegel, L., Kasahara, H., Izumo, S., Komuro, I., Agellon, L. B., and Michalak, M. (2001) COUP-TF1 antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development. J Biol Chem 276, 2797-2801. 11106640

  107. Dibrov, P., Murtazina, R., Kinsella, J., and Fliegel, L. (2000) Characterization of a histidine rich cluster of amino acids in the cytoplasmic domain of the Na+/H+ exchanger. Biosci Rep 20, 185-197. 11095118

  108. Moor, A. N., Murtazina, R., and Fliegel, L. (2000) Calcium and osmotic regulation of the Na+/H+ exchanger in neonatal ventricular myocytes. J Mol Cell Cardiol 32, 925-936. 10888247

  109. Fliegel, L. (1999) Functional and cellular regulation of the myocardial Na+/H+ exchanger. J Thromb Thrombolysis 8, 9-14. 10481209

  110. Moor, A. N., and Fliegel, L. (1999) Protein kinase-mediated regulation of the Na(+)/H(+) exchanger in the rat myocardium by mitogen-activated protein kinase-dependent pathways. J Biol Chem 274, 22985-22992. 10438464

  111. Gebreselassie, D., Rajarathnam, K., and Fliegel, L. (1998) Expression, purification, and characterization of the carboxyl-terminal region of the Na+/H+ exchanger. Biochem Cell Biol 76, 837-842. 10353718

  112. Fliegel, L., Murtazina, R., Dibrov, P., Harris, C., Moor, A., and Fernandez-Rachubinski, F. A. (1998) Regulation and characterization of the Na+/H+ exchanger. Biochem Cell Biol 76, 735-741. 10353706

  113. Harris, C., and Fliegel, L. (1999) Amiloride and the Na(+)/H(+) exchanger protein: mechanism and significance of inhibition of the Na(+)/H(+) exchanger (review). Int J Mol Med 3, 315-321. 10028059

  114. Wang, H., Singh, D., and Fliegel, L. (1998) Functional role of cysteine residues in the Na+/H+ exchanger effects of mutation of cysteine residues on targeting and activity of the Na+/H+ exchanger. Arch Biochem Biophys 358, 116-124. 9750172

  115. Dibrov, P., Young, P. G., and Fliegel, L. (1998) Physiological consequences of expression of the Na+/H+ antiporter sod2 in Escherichia coli. Mol Cell Biochem 183, 125-132. 9655186

  116. Dibrov, P., Young, P. G., and Fliegel, L. (1998) Functional analysis of amino acid residues essential for activity in the Na+/H+ exchanger of fission yeast. Biochemistry 37, 8282-8288. 9622480

  117. Dibrov, P., and Fliegel, L. (1998) Comparative molecular analysis of Na+/H+ exchangers: a unified model for Na+/H+ antiport? FEBS Lett 424, 1-5. 9537504

  118. Besson, P., Fernandez-Rachubinski, F., Yang, W., and Fliegel, L. (1998) Regulation of Na+/H+ exchanger gene expression: mitogenic stimulation increases NHE1 promoter activity. Am J Physiol 274, C831-839. 9530116

  119. Wang, H., Yang, W., and Fliegel, L. (1997) Identification of an HMG-like protein involved in regulation of Na+/H+ exchanger expression. Mol Cell Biochem 176, 99-106. 9406150

  120. Wang, H., Lemire, B. D., Cass, C. E., Weiner, J. H., Michalak, M., Singh, D., and Fliegel, L. (1997) Interactions of a high mobility group-like protein with human mitochondrial DNA. Arch Biochem Biophys 346, 193-202. 9343366

  121. Wang, H., Singh, D., and Fliegel, L. (1997) The Na+/H+ antiporter potentiates growth and retinoic acid-induced differentiation of P19 embryonal carcinoma cells. J Biol Chem 272, 26545-26549. 9334233

  122. Fliegel, L., and Wang, H. (1997) Regulation of the Na+/H+ exchanger in the mammalian myocardium. J Mol Cell Cardiol 29, 1991-1999. 9281433

  123. Wang, H., Silva, N. L., Lucchesi, P. A., Haworth, R., Wang, K., Michalak, M., Pelech, S., and Fliegel, L. (1997) Phosphorylation and regulation of the Na+/H+ exchanger through mitogen-activated protein kinase. Biochemistry 36, 9151-9158. 9230047

  124. Silva, N. L., Wang, H., Harris, C. V., Singh, D., and Fliegel, L. (1997) Characterization of the Na+/H+ exchanger in human choriocarcinoma (BeWo) cells. Pflugers Arch 433, 792-802. 9049172

  125. Dibrov, P., Smith, J. J., Young, P. G., and Fliegel, L. (1997) Identification and localization of the sod2 gene product in fission yeast. FEBS Lett 405, 119-124. 9094438

  126. Wang, H., Singh, D., Yang, W., Dyck, J. R., and Fliegel, L. (1996) Structure and analysis of the mouse Na+/H+ exchanger (NHE1) gene: homology and conservation of splice sites. Mol Cell Biochem 165, 155-159. 8979265

  127. Yang, W., Wang, H., and Fliegel, L. (1996) Regulation of Na+/H+ exchanger gene expression. Role of a novel poly(dA.dT) element in regulation of the NHE1 promoter. J Biol Chem 271, 20444-20449. 8702783

  128. Wang, H., Lemire, B. D., Cass, C. E., Weiner, J. H., Michalak, M., Penn, A. M., and Fliegel, L. (1996) Zidovudine and dideoxynucleosides deplete wild-type mitochondrial DNA levels and increase deleted mitochondrial DNA levels in cultured Kearns-Sayre syndrome fibroblasts. Biochim Biophys Acta 1316, 51-59. 8634344

  129. Yang, W., Dyck, J. R., and Fliegel, L. (1996) Regulation of NHE1 expression in L6 muscle cells. Biochim Biophys Acta 1306, 107-113. 8611615

  130. Yang, W., Dyck, J. R., Wang, H., and Fliegel, L. (1996) Regulation of NHE-1 promoter in mammalian myocardium. Am J Physiol 270, H259-266. 8769760

  131. Shaw, A. R., Domanska, A., Mak, A., Gilchrist, A., Dobler, K., Visser, L., Poppema, S., Fliegel, L., Letarte, M., and Willett, B. J. (1995) Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation. J Biol Chem 270, 24092-24099. 7592610

  132. Silva, N. L., Haworth, R. S., Singh, D., and Fliegel, L. (1995) The carboxyl-terminal region of the Na+/H+ exchanger interacts with mammalian heat shock protein. Biochemistry 34, 10412-10420. 7654695

  133. Dyck, J. R., and Fliegel, L. (1995) Specific activation of the Na+/H+ exchanger gene during neuronal differentiation of embryonal carcinoma cells. J Biol Chem 270, 10420-10427. 7737975

  134. Dyck, J. R., Maddaford, T. G., Pierce, G. N., and Fliegel, L. (1995) Induction of expression of the sodium-hydrogen exchanger in rat myocardium. Cardiovasc Res 29, 203-208. 7736496

  135. Fliegel, L., and Dyck, J. R. (1995) Molecular biology of the cardiac sodium/hydrogen exchanger. Cardiovasc Res 29, 155-159. 7736488

  136. Dyck, J. R., Silva, N. L., and Fliegel, L. (1995) Activation of the Na+/H+ exchanger gene by the transcription factor AP-2. J Biol Chem 270, 1375-1381. 7836405

  137. Wang, H., Fliegel, L., Cass, C. E., Penn, A. M., Michalak, M., Weiner, J. H., and Lemire, B. D. (1994) Quantification of mitochondrial DNA in heteroplasmic fibroblasts with competitive PCR. Biotechniques 17, 76-78, 80, 82. 7946321

  138. Fliegel, L., and Frohlich, O. (1993) The Na+/H+ exchanger: an update on structure, regulation and cardiac physiology. Biochem J 296 ( Pt 2), 273-285. 8257412

  139. Fliegel, L., Dyck, J. R., Wang, H., Fong, C., and Haworth, R. S. (1993) Cloning and analysis of the human myocardial Na+/H+ exchanger. Mol Cell Biochem 125, 137-143. 8283968

  140. Haworth, R. S., and Fliegel, L. (1993) Intracellular pH in Schizosaccharomyces pombe--comparison with Saccharomyces cerevisiae. Mol Cell Biochem 124, 131-140. 8232284

  141. Haworth, R. S., Cragoe, E. J., Jr., and Fliegel, L. (1993) Amiloride and 5-(N-ethyl-N-isopropyl) amiloride inhibit medium acidification and glucose metabolism by the fission yeast Schizosaccharomyces pombe. Biochim Biophys Acta 1145, 266-272. 8431459

  142. Haworth, R. S., Frohlich, O., and Fliegel, L. (1993) Multiple carbohydrate moieties on the Na+/H+ exchanger. Biochem J 289 ( Pt 3), 637-640. 8382044

  143. Fliegel, L., Haworth, R. S., and Dyck, J. R. (1993) Characterization of the placental brush border membrane Na+/H+ exchanger: identification of thiol-dependent transitions in apparent molecular size. Biochem J 289 ( Pt 1), 101-107. 8380978

  144. Dyck, J. R., Lopaschuk, G. D., and Fliegel, L. (1992) Identification of a small Na+/H+ exchanger-like message in the rabbit myocardium. FEBS Lett 310, 255-259. 1327873

  145. Fliegel, L., Walsh, M. P., Singh, D., Wong, C., and Barr, A. (1992) Phosphorylation of the C-terminal domain of the Na+/H+ exchanger by Ca2+/calmodulin-dependent protein kinase II. Biochem J 282 ( Pt 1), 139-145. 1311552

  146. Haworth, R. S., Lemire, B. D., Crandall, D., Cragoe, E. J., Jr., and Fliegel, L. (1991) Characterisation of proton fluxes across the cytoplasmic membrane of the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1098, 79-89. 1661160

  147. Opas, M., Dziak, E., Fliegel, L., and Michalak, M. (1991) Regulation of expression and intracellular distribution of calreticulin, a major calcium binding protein of nonmuscle cells. J Cell Physiol 149, 160-171. 1939344

  148. Fliegel, L., and Michalak, M. (1991) Fast-twitch and slow-twitch skeletal muscles express the same isoform of calreticulin. Biochem Biophys Res Commun 177, 979-984. 2059224

  149. Hogue, D., Michalak, M., and Fliegel, L. (1991) The role of ion antiporters in the maintenance of intracellular pH in rat vascular smooth muscle cells. Mol Cell Biochem 102, 125-137. 1652679

  150. Fliegel, L., Sardet, C., Pouyssegur, J., and Barr, A. (1991) Identification of the protein and cDNA of the cardiac Na+/H+ exchanger. FEBS Lett 279, 25-29. 1704856

  151. Fliegel, L., Newton, E., Burns, K., and Michalak, M. (1990) Molecular cloning of cDNA encoding a 55-kDa multifunctional thyroid hormone binding protein of skeletal muscle sarcoplasmic reticulum. J Biol Chem 265, 15496-15502. 1697592

  152. Michalak, M., Fliegel, L., and Wlasichuk, K. (1990) Isolation and characterization of calcium binding glycoproteins of cardiac sarcolemmal vesicles. J Biol Chem 265, 5869-5874. 2108150

  153. Fliegel, L., Burns, K., MacLennan, D. H., Reithmeier, R. A., and Michalak, M. (1989) Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum. J Biol Chem 264, 21522-21528. 2600080

  154. Fliegel, L., Burns, K., Wlasichuk, K., and Michalak, M. (1989) Peripheral membrane proteins of sarcoplasmic and endoplasmic reticulum. Comparison of carboxyl-terminal amino acid sequences. Biochem Cell Biol 67, 696-702. 2686719

  155. Fliegel, L., Burns, K., Opas, M., and Michalak, M. (1989) The high-affinity calcium binding protein of sarcoplasmic reticulum. Tissue distribution, and homology with calregulin. Biochim Biophys Acta 982, 1-8. 2663080

  156. Fliegel, L., Leberer, E., Green, N. M., and MacLennan, D. H. (1989) The fast-twitch muscle calsequestrin isoform predominates in rabbit slow-twitch soleus muscle. FEBS Lett 242, 297-300. 2914612

  157. Zarain-Herzberg, A., Fliegel, L., and MacLennan, D. H. (1988) Structure of the rabbit fast-twitch skeletal muscle calsequestrin gene. J Biol Chem 263, 4807-4812. 2832408

  158. Brandl, C. J., Fliegel, L., and MacLennan, D. H. (1988) cDNA cloning of sarcoplasmic reticulum proteins. Methods Enzymol 157, 289-302. 3231089

  159. Fliegel, L., Ohnishi, M., Carpenter, M. R., Khanna, V. K., Reithmeier, R. A., and MacLennan, D. H. (1987) Amino acid sequence of rabbit fast-twitch skeletal muscle calsequestrin deduced from cDNA and peptide sequencing. Proc Natl Acad Sci U S A 84, 1167-1171. 3469659

  160. Fliegel, L., and Drummond, G. (1985) Beta-adrenergic stimulation of sarcolemmal phosphorylation in the perfused rabbit heart. Can J Cardiol 1, 318-327. 3021302

  161. Fliegel, L., Takeo, S., Beamish, R. E., and Dhalla, N. S. (1985) Adrenochrome uptake and subcellular distribution in the isolated perfused rat heart. Can J Cardiol 1, 122-127. 3850768

  162. Fliegel, L., and Drummond, G. I. (1985) Effect of forskolin on phosphorylation of a 25,000 Mr protein in perfused guinea pig hearts. J Cyclic Nucleotide Protein Phosphor Res 10, 259-267. 4040533

  163. Karmazyn, M., Beamish, R. E., Fliegel, L., and Dhalla, N. S. (1981) Adrenochrome-induced coronary artery constriction in the rat heart. J Pharmacol Exp Ther 219, 225-230. 6793711

  164. Takeo, S., Fliegel, L., Beamish, R. E., and Dhalla, N. S. (1980) Effects of adrenochrome on rat heart sarcolemmal ATPase activities. Biochem Pharmacol 29, 559-564. 6245655
Our Research

Our laboratory studies the regulation of intracellular pH and the removal of excess intracellular acid. In mammalian tissues the main protein responsible for this is the Na+/H+ exchanger.

Who We Are

Larry Fliegel, Principal Investigator

Contact Us

Dr. Larry Fliegel
Professor
Associate Chair, Department of Biochemistry

Ph.D., University of Calgary

Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
347 Medical Sciences Building
Edmonton, Alberta, Canada  T6G 2H7

Tel: 780.492.1848
Lab Tel: 780.492.1847
Fax: 780.492.0886

Email Dr. Fliegel

Data Deposits

© 2018 Department of Biochemistry University of Alberta