Pathophysiological consequences of homocysteine excess

Journal of Nutrition

Volumn 136, Issue 6, 2006, Pages

  Jakubowski, Hieronim ^a,b  

^a RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^b POLISH ACADEMY OF SCIENCES   (Poland)

Author keywords

Autoimmune response; Cardiovascular disease; Cellular toxicity; Homocysteine thiolactone; N homocysteinylated protein

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ALBUMIN; AUTOANTIBODY; FIBRINOGEN; HEMOGLOBIN; HOMOCYSTEINE; HOMOCYSTEINE THIOLACTONE;

APOPTOSIS; ATHEROSCLEROSIS; AUTOIMMUNITY; BLISTER; CATALYSIS; CHEMICAL STRUCTURE; CONFERENCE PAPER; CYTOTOXICITY; DESQUAMATION; DIETARY INTAKE; ENZYME INACTIVATION; GAS CHROMATOGRAPHY; GROWTH RETARDATION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MASS SPECTROMETRY; METABOLITE; NEUROTOXICITY; NONHUMAN; SEIZURE; SOMITE; STROKE;

EID: 33646788784     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.1093/jn/136.6.1741s     Document Type: Conference Paper

References (70)

1. Harper AE, Benevenga NJ, Wohlheuter RM. Effects of ingestion of disproportionate amounts of amino acids. Physiol Rev. 1970;50:428-58.
2. Benevenga NJ, Steele RD. Adverse effects of excessive consumption of amino acids. Annu Rev Nutr. 1984;4:157-81.
3. Matsueda S, Niiyama Y. The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats. J Nutr Sci Vitaminol (Tokyo). 1982;28:557-73.
4. Fau D, Preret J, Hadjiisky P. Effects of ingestion of high protein or excess methionine diets by rats for two years. J Nutr. 1988;118:128-33.
5. Carson NA, Custworth DC, Dent CE, Field CM, Neill DW, Westall RG. Homocystinuria: A new inborn error of metabolism associated with mental deficiency. Arch Dis Child. 1963;38:425-36.
6. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GH, Bromberg IL, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet. 1985;37:1-31.
7. McCully KS. Vascular pathology of hyperhomocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969;56:111-28.
8. Lentz SR. Mechanisms of homocysteine-induced atherothrombosis. J Thromb Haemost. 2005;3:1646-54.
9. Jakubowski H. Molecular basis of homocysteine toxicity in humans. Cell Mol Life Sci. 2004;61:470-87.
10. Jakubowski H. Translational accuracy of aminoacyl-tRNA synthetases: Implications for atherosclerosis. J Nutr. 2001;131 suppl:2983-7.
11. Jakubowski H, Goldman E. Synthesis of homocysteine thiolactone by methionyl-tRNA synthetase in cultured mammalian cells. FEBS Lett. 1993;317:237-40.
12. Jakubowski H. Metabolism of homocysteine thiolactone in human cell cultures: Possible mechanism for pathological consequences of elevated homocysteine levels. J Biol Chem. 1997;272:1935-41.
13. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: Implications for atherosclerosis. Circ Res. 2000;87:45-51.
14. Jakubowski H. Protein homocysteinylation: Possible mechanism underlying pathological consequences of elevated homocysteine levels. FASEB J. 1999;13:2277-83.
15. Jakubowski H. Homocysteine is a protein amino acid in humans: Implications for homocysteine-linked disease. J Biol Chem. 2002;277:30425-8.
16. Głowacki R, Jakubowski H. Cross-talk between cys34 and lysine residues in human serum albumin revealed by N-homocysteinylation. J Biol Chem. 2004;279:10864-71.
17. Jakubowski H. Anti-N-homocysteinylated protein auto-antibodies and cardiovascular disease. Clin Chem Lab Med. 2005;43:1011-4.
18. Jakubowski H. The determination of homocysteine-thiolactone in biological samples. Anal Biochem. 2002;308:112-9.
19. Chwatko G, Jakubowski H. The determination of homocysteine-thiolactone in human plasma. Anal Biochem. 2005;337:271-7.
20. Chwatko G, Jakubowski H. Urinary excretion of homocysteine-thiolactone in humans. Clin Chem. 2005;51:408-15.
21. Mukai Y, Togawa T, Suzuki T, Ohata K, Tanabe S. Determination of homocysteine thiolactone and homocysteine in cell cultures using high-performance liquid chromatography with fluorescence detection. J Chromatogr B. 2002;767:263-8.
22. Guttormsen AB, Mansoor MA, Fiskerstrand T, Ueland PM, Refsum H. Kinetics of plasma homocysteine in healthy subjects after peroral loading. Clin Chem. 1993;39:1390-7.
23. Daneshvar P, Yazdanpanah M, Cuthbert C, Cole DE. Quantitative assay of plasma homocysteine thiolactone by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2003;17:258-62.
24. Harker LA, Slichter SJ, Scott CR, Ross R. Homocystinemia: Vascular injury and arterial thrombosis. N Engl J Med. 1974;291:537-41.
25. Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced injury and atherosclerosis in baboons. Circ Res. 1983;53:731-8.
26. Donahue S, Sturman JA, Gaul G. Arteriosclerosis due to homocysteinemia: Failure to reproduce the model in weaning rabbits. Am J Pathol. 1974;77:167-74.
27. Makheja AN, Bombard RL, Randazzo RL, Bailey JM. Anti-inflamatory drugs in experimental atherosclerosis. Part 3. Evaluation of the atherogenicity of homocysteine in rabbits. Atherosclerosis. 1978;29:105-12.
28. Reddy GS, Wilcken DE. Experimental homocysteinemia in pigs: comparison with studies in sixteen homocystinuric patients. Metabolism. 1982;31:778-83.
29. Jakubowski H. Calcium-dependent human serum homocysteine thiolactone hydrolase: A protective mechanism against protein N-homocysteinylation. J Biol Chem. 2000;275:3957-62.
30. Jakubowski H, Ambrosius W, Pratt JH. Genetic determinants of homocysteine thiolactonase activity in humans: Implications for atherosclerosis. FEBS Lett. 2001;491:35-9.
31. Jakubowski H. Biosynthesis and reactions of homocysteine thiolactone. In: Jacobson D, Carmel R, editors. Homocysteine in health and disease. Cambridge, UK: Cambridge University Press; 2001. p. 21-31.
32. Zimny J, Iwanowska D, Starzynska E, Jakubowski H, Guranowski A. Homocysteine thiolactone is a substrate of bleomycine hydrolase/cysteine protease/gal6 protein. Clin Chem Lab Med. 2005;43:A23.
33. Perdziak M, Zimny J, Jakubowski H, Guranowski A. Human placental protein purified as homocysteine-thiolactone hydrolase has been identified as human bleomycin hydrolase. [abstract] Acta Biochim Pol. 2005;50: Suppl. 1:184.
34. Folbergrova J. Anticonvulsant action of both NMDA and non-NMDA receptor antagonists against seizures induced by homocysteine in immature rats. Exp Neurol. 1997;145:442-50.
35. Langmeier M, Folbergrova J, Haugvicova R, Pokorny J, Mares P. Neuronal cell death in hippocampus induced by homocysteic acid in immature rats. Epilepsia. 2003;44:299-304.
36. Spence AM, Rasey JS, Dwyer-Hansen L, Grunbaum Z, Livesey J, Chin L, Nelson N, Stein D, Krohn KA, Ali-Osman F. Toxicity, biodistribution and radioprotective capacity of L-homocysteine thiolactone in CNS tissues and tumors in rodents: comparison with prior results with phosphorothioates. Radiother Oncol. 1995;35:216-26.
37. Frauscher G, Karnaukhova E, Muehl A, Hoeger H, Lubec B. Oral administration of homocysteine leads to increased plasma triglycerides and homocysteic acid-additional mechanisms in homocysteine induced endothelial damage? Life Sci. 1995;57:813-7.
38. Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Arnelle DR, Stamler JS. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci USA. 1997;94:5923-8.
39. Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26:137-46.
40. Greene ND, Dunlevy LE, Copp AJ. Homocysteine is embryotoxic but does not cause neural tube defects in mouse embryos. Anat Embryol (Berl). 2003;206:185-91.
41. Van Aertes LA, Klaasboer HH, Postma NS, Pertijs JC, Peereboom JH, Eskes TK, Noordhoek J. Stereospecific in vitro embryotoxicity of L-homocysteine in pre- and post-implantation rodent embryos. Toxicol In Vitro. 1993;6:743-9.
42. Rosenquist TH, Ratashak SA, Selhub J. Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid. Proc Natl Acad Sci USA. 1996;93:15227-32.
43. Hansen DK, Grafton F, Melnyk S, James JS. Lack of embryotoxicity of homocysteine thiolactone in mouse embryos in vitro. Reprod Toxicol. 2001;15:239-44.
44. Mercie P, Garnier O, Lascoste L, Renard M, Closse C, Durrieu F, Marit G, Boisseau RM, Belloc F. Homocysteine thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features. Apoptosis. 2000;5:403-11.
45. Huang RF, Huang SM, Lin BS, Wei JS, Liu TZ. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci. 2001;68:2799-811.
46. Kamudhamas A, Pang L, Smith DA, Sadovsky Y, Nelson DM. Homocysteine thiolactone induces apoptosis in cultured human trophoblasts: A potential mechanism for homocysteine-mediated placental dysfunction? Am J Obstet Gynecol. 2004;191:563-71.
47. Najib S, Sanchez-Margalet V. Homocysteine thiolactone inhibits insulin-stimulated DNA and protein synthesis: possible role of mitogen-activated protein kinase (MAPK), glycogen synthase kinase-3 (GSK-3) and p70 S6K phosphorylation. J Mol Endocrinol. 2005;34:119-26.
48. Zhang C, Cai Y, Adachi MT, Oshiro S, Aso T, Kaufman RJ, Kitajima ST. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem. 2001;276:35867-74.
49. Roybal CN, Yang S, Sun CW, Hurtado D, Vander Jagt DL, Townes TM, Abcouwer SF. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J Biol Chem. 2004;279:14844-52.
50. Mudd SH, Finkelstein JD, Refsum H, Ueland PM, Malinow MR, Lentz SR, Jacobsen DW, Brattstrom L, Wilcken B, et al. Homocysteine and its disulfide derivatives: a suggested consensus terminology. Arterioscler Thromb Vasc Biol. 2000;20:1704-6.
51. Uji Y, Motomiya Y, Hanyu N, Ukaji F, Okabe H. Protein-bound homocystamide measured in human plasma by HPLC. Clin Chem. 2002;48:941-4.
52. Sass JO, Nakanishi T, Sato T, Sperl W, Shimizu A. S-Homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia. Biochem Biophys Res Commun. 2003;310:242-6.
53. 1H-NMR spectroscopy. Eur J Biochem. 1994;225:363-8.
54. Sauls DL, Lockhart E, Hoffman M. Reaction of fibrinogen with homocysteine thiolactone renders the resulting fibrin clots resistant to lysis. [abstract] J Thromb Haemost. 2005;3: suppl. 1:OR130.
55. Hop CE, Bakhtiar R. Homocysteine thiolactone and protein homocysteinylation: mechanistic studies with model peptides and proteins. Rapid Commun Mass Spectrom. 2002;16:1049-53.
56. Naruszewicz M, Mirkiewicz E, Olszewski AJ, McCully KS. Thiolation of low density lipoprotein by homocysteine thiolactone causes increased aggregation and altered interaction with cultured macrophages. Nutr Metab Cardiovasc Dis. 1994;4:70-7.
57. Vidal M, Sainte-Marie J, Philippot J, Bienvenue A. T. Thiolation of low-density lipoproteins and their interaction with L2C leukemic lymphocytes. Biochimie. 1986;68:723-30.
58. Ferguson E, Hogg N, Antholine WE, Joseph J, Singh RJ, Parthasarathy S, Kalyanaraman BT. Characterization of the adduct formed from the reaction between homocysteine thiolactone and low-density lipoprotein: antioxidant implications. Free Radic Biol Med. 1999;26:968-77.
59. Liu G, Nellaiappan K, Kagan HM. Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. J Biol Chem. 1997;272:32370-7.
60. Raposo B, Rodriguez C, Martinez-Gonzalez J, Badimon L. High levels of homocysteine inhibit lysyl oxidase (LOX) and downregulate LOX expression in vascular endothelial cells. Atherosclerosis. 2004;177:1-8.
61. Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers GH. Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria. Biochim Biophys Acta. 1996;1315:159-62.
62. Maki JM, Rasanen J, Tikkanen H, Sormunen R, Makikallio K, Kivirikko KI, Soininen R. Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Circulation. 2002;106:2503-9.
63. Ferguson E, Parthasarathy S, Joseph J, Kalyanaraman B. Generation and initial characterization of a novel polyclonal antibody directed against homocysteine thiolactone-modified low-density lipoprotein. J Lipid Res. 1998;39:925-33.
64. Undas A, Perła J, Łaciński M, Trzeciak W, Kaźmierski R, Jakubowski H. Autoantibodies against N-homocysteinylated proteins in humans: Implications for atherosclerosis. Stroke. 2004;35:1299-304.
65. ω-homocysteinyl-aminohexyl-Agarose. J Chromatogr B. 2004;807:257-61.
66. Undas A, Jankowski M, Twardowska M, Padjas A, Jakubowski H, Szczeklik A. Antibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in men. Thromb Haemost. 2005;93:346-50.
67. Stefani M. Protein misfolding and aggregation: new examples in medicine and biology of the dark side of the protein world. Biochim Biophys Acta. 2004;1739:5-25.
68. Ferretti G, Bacchetti T, Moroni C, Vignini A, Nanetti L, Curatola G. Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells. J Cell Biochem. 2004;92:351-60.
69. Vignini A, Nanetti L, Bacchetti T, Ferretti G, Curatola G, Mazanti L. Modification induced by homocysteine and low-density lipoprotein on human aortic endothelial cells: An in vitro study. J Clin Endocrinol Metab. 2004;89:4558-61.
70. Austin RC, Lentz SR, Werstuck GH. Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ. 2004;11:Suppl 1:S56-64.