Cell type-specific recycling of tetrahydrobiopterin by dihydrofolate reductase explains differential effects of 7,8-dihydrobiopterin on endothelial nitric oxide synthase uncoupling

Biochemical Pharmacology

Volumn 90, Issue 3, 2014, Pages 246-253

  Schmidt, Kurt ^a   Kolesnik, Bernd ^a   Gorren, Antonius C F ^a   Werner, Ernst R ^b   Mayer, Bernd ^a  

^a UNIVERSITY OF GRAZ   (Austria)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Dihydrofolate reductase; Endothelial nitric oxide synthase uncoupling; Human endothelial cells; Porcine endothelial cells; Tetrahydrobiopterin recycling

Indexed keywords

DIHYDROBIOPTERIN; DIHYDROFOLATE REDUCTASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; TETRAHYDROBIOPTERIN;

ANIMAL CELL; AORTA; ARTICLE; BINDING AFFINITY; CATALYSIS; CELL ISOLATION; CELL SPECIFICITY; CONTROLLED STUDY; CYTOSOL; ENDOTHELIAL NITRIC OXIDE SYNTHASE UNCOUPLING; ENDOTHELIUM CELL; ENZYME ACTIVITY; ENZYME KINETICS; ENZYME REGULATION; HUMAN; HUMAN CELL; MICROVASCULAR ENDOTHELIAL CELL; NONHUMAN; PRIORITY JOURNAL; RECYCLING; REDUCTION; TETRAHYDROBIOPTERIN RECYCLING; UMBILICAL VEIN ENDOTHELIAL CELL;

DIHYDROFOLATE REDUCTASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE UNCOUPLING; HUMAN ENDOTHELIAL CELLS; PORCINE ENDOTHELIAL CELLS; TETRAHYDROBIOPTERIN RECYCLING;

ANIMALS; AORTA; BIOPTERIN; CELL LINE; CELLS, CULTURED; CYCLIC GMP; DERMIS; ENDOTHELIUM, VASCULAR; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; MICROVESSELS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; OXIDATION-REDUCTION; REACTIVE OXYGEN SPECIES; SUPEROXIDES; SUS SCROFA; TETRAHYDROFOLATE DEHYDROGENASE;

EID: 84903902258     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2014.05.010     Document Type: Article

References (35)

1. A.C.F. Gorren, and B. Mayer Nitric-oxide synthase: a cytochrome P450 family foster child Biochim Biophys Acta 1770 2007 432 445 (Pubitemid 46136746)
2. T.S. Schmidt, and N.J. Alp Mechanisms for the role of tetrahydrobiopterin in endothelial function and vascular disease Clin Sci (Lond) 113 2007 47 63 (Pubitemid 47066025)
3. J. Vasquez-Vivar Tetrahydrobiopterin, superoxide, and vascular dysfunction Free Radic Biol Med 47 2009 1108 1119
4. U. Förstermann Nitric oxide and oxidative stress in vascular disease Pflugers Arch 459 2010 923 939
5. M.J. Crabtree, C.L. Smith, G. Lam, M.S. Goligorsky, and S.S. Gross Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS Am J Physiol Heart Circ Physiol 294 2008 H1530 H1540
6. P. Klatt, M. Schmid, E. Leopold, K. Schmidt, E.R. Werner, and B. Mayer The pteridine binding site of brain nitric oxide synthase: tetrahydrobiopterin binding kinetics, specificity, and allosteric interaction with the substrate domain J Biol Chem 269 1994 13861 13866
7. A. Presta, U. Siddhanta, C. Wu, N. Sennequier, L. Huang, and H.M. Abu-Soud et al. Comparative functioning of dihydro- and tetrahydropterins in supporting electron transfer, catalysis, and subunit dimerization in inducible nitric oxide synthase Biochemistry 37 1998 298 310 (Pubitemid 28049133)
8. E.R. Werner, N. Blau, and B. Thöny Tetrahydrobiopterin: biochemistry and pathophysiology Biochem J 438 2011 397 414
9. M.J. Crabtree, and K.M. Channon Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease Nitric Oxide 25 2011 81 88
10. K. Chalupsky, and H. Cai Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase Proc Natl Acad Sci U S A 102 2005 9056 9061 (Pubitemid 40881077)
11. M.J. Crabtree, A.L. Tatham, A.B. Hale, N.J. Alp, and K.M. Channon Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways J Biol Chem 284 2009 28128 28136
12. T. Sugiyama, B.D. Levy, and T. Michel Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells J Biol Chem 284 2009 12691 12700
13. M.J. Crabtree, A.B. Hale, and K.M. Channon Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency Free Radic Biol Med 50 2011 1639 1646
14. J. Whitsett, A. Rangel Filho, S. Sethumadhavan, J. Celinska, M. Widlansky, and J. Vasquez-Vivar Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling Free Radic Biol Med 63C 2013 143 150
15. P. Klatt, S. Pfeiffer, B.M. List, D. Lehner, O. Glatter, and H.P. Bächinger et al. Characterization of heme-deficient neuronal nitric-oxide synthase reveals a role for heme in subunit dimerization and binding of the amino acid substrate and tetrahydrobiopterin J Biol Chem 271 1996 7336 7342 (Pubitemid 26106999)
16. K. Schmidt, B. Mayer, and W.R. Kukovetz Effect of calcium on endothelium-derived relaxing factor formation and cGMP levels in endothelial cells Eur J Pharmacol 170 1989 157 166 (Pubitemid 19274643)
17. C. Meda, C. Plank, O. Mykhaylyk, K. Schmidt, and B. Mayer Effects of statins on nitric oxide/cGMP signaling in human umbilical vein endothelial cells Pharmacol Rep 62 2010 100 112
18. E.W. Ades, F.J. Candal, R.A. Swerlick, V.G. George, S. Summers, and D.C. Bosse et al. HMEC-1: establishment of an immortalized human microvascular endothelial cell line J Invest Dermatol 99 1992 683 690 (Pubitemid 23002027)
19. K. Schmidt, G. Werner-Felmayer, B. Mayer, and E.R. Werner Preferential inhibition of inducible nitric oxide synthase in intact cells by the 4-amino analogue of tetrahydrobiopterin Eur J Biochem 259 1999 25 31 (Pubitemid 29030814)
20. T. Fukushima, and J.C. Nixon Analysis of reduced forms of biopterin in biological tissues and fluids Anal Biochem 102 1980 176 188 (Pubitemid 10099498)
21. K. Schmidt, A. Neubauer, B. Kolesnik, J.P. Stasch, E.R. Werner, and A.C. Gorren et al. Tetrahydrobiopterin protects soluble guanylate cyclase against oxidative inactivation Mol Pharmacol 82 2012 420 427
22. J.F. Reinhard Jr., J.Y. Chao, G.K. Smith, D.S. Duch, and C.A. Nichol A sensitive high-performance liquid chromatographic-fluorometric assay for dihydrofolate reductase in adult rat brain, using 7,8-dihydrobiopterin as substrate Anal Biochem 140 1984 548 552 (Pubitemid 14071964)
23. L. Gao, K. Chalupsky, E. Stefani, and H. Cai Mechanistic insights into folic acid-dependent vascular protection: dihydrofolate reductase (DHFR)-mediated reduction in oxidant stress in endothelial cells and angiotensin II-infused mice: a novel HPLC-based fluorescent assay for DHFR activity J Mol Cell Cardiol 47 2009 752 760
24. E.R. Werner, E. Pitters, K. Schmidt, H. Wachter, G. Werner-Felmayer, and B. Mayer Indentification of the 4-amino analog of tetrahydrobiopterin as dihydropteridine reductase inhibitor and potent pteridine antagonist of rat neuronal nitric oxide synthase Biochem J 320 1996 193 196 (Pubitemid 26400179)
25. S. Pfeiffer, A.C.F. Gorren, E. Pitters, K. Schmidt, E.R. Werner, and B. Mayer Allosteric modulation of rat brain nitric oxide synthase by the pterin-site enzyme inhibitor 4-amino-tetrahydrobiopterin Biochem J 328 1997 349 352 (Pubitemid 27515572)
26. S. Moncada, D.D. Rees, R. Schulz, and R.M. Palmer Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo Proc Natl Acad Sci U S A 88 1991 2166 2170 (Pubitemid 21916375)
27. B.M. List, B. Klösch, C. Völker, A.C.F. Gorren, W.C. Sessa, and E.R. Werner et al. Characterization of bovine endothelial nitric oxide synthase as a homodimer with down-regulated uncoupled NADPH oxidase activity: tetrahydrobiopterin binding kinetics and role of haem in dimerization Biochem J 323 1997 159 165 (Pubitemid 27153889)
28. H. Hasegawa, K. Sawabe, N. Nakanishi, and O.K. Wakasugi Delivery of exogenous tetrahydrobiopterin (BH4) to cells of target organs: role of salvage pathway and uptake of its precursor in effective elevation of tissue BH4 Mol Genet Metab 86 Suppl. 1 2005 S2 S10
29. K. Schmidt, E.R. Werner, B. Mayer, H. Wachter, and W.R. Kukovetz Tetrahydrobiopterin-dependent formation of endothelium-derived relaxing factor (nitric oxide) in aortic endothelial cells Biochem J 281 1992 297 300
30. G. Werner-Felmayer, E.R. Werner, D. Fuchs, A. Hausen, G. Reibnegger, and K. Schmidt et al. Pteridine biosynthesis in human endothelial cells - impact on nitric oxide-mediated formation of cyclic GMP J Biol Chem 268 1993 1842 1846 (Pubitemid 23033583)
31. R. Heller, A. Unbehaun, B. Schellenberg, B. Mayer, G. Werner-Felmayer, and E.R. Werner l-Ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin J Biol Chem 276 2001 40 47 (Pubitemid 32050286)
32. T.A. Baker, S. Milstien, and Z.S. Katusic Effect of vitamin C on the availability of tetrahydrobiopterin in human endothelial cells J Cardiovasc Pharmacol 37 2001 333 338 (Pubitemid 32193512)
33. A.S. Tibbetts, and D.R. Appling Compartmentalization of mammalian folate-mediated one-carbon metabolism Annu Rev Nutr 30 2010 57 81
34. D.D. Anderson, C.F. Woeller, and P.J. Stover Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase Clin Chem Lab Med 45 2007 1760 1763 (Pubitemid 350232980)
35. C.F. Woeller, D.D. Anderson, D.M. Szebenyi, and P.J. Stover Evidence for small ubiquitin-like modifier-dependent nuclear import of the thymidylate biosynthesis pathway J Biol Chem 282 2007 17623 17631 (Pubitemid 47100287)