• 1
    Cattaneo, M. (1999) Hyperhomocysteinemia, atherosclerosis and thrombosis. Thromb. Haemost. 81, 165176.
  • 2
    Malinow, M.R., Kang, S.S., Taylor, L.M., Wong, P.W., Coull, B., Inahara, T., Mukerjee, D., Sexton, G. & Upson, B. (1989) Prevalence of hyperhomocystinemia in patients with peripheral arterial occlusive disease. Circulation 79, 11801188.
  • 3
    Verhoef, P., Stampfer, M.J., Buring, J.E., Gaziano, J.M., Allen, R.H., Stabler, S.P., Reynolds, R.D., Kok, F.J., Hennekens, C.H. & Willett, W.C. (1996) Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am. J. Epidemiol. 143, 845859.
  • 4
    Clarke, R., Smith, A.D., Jobst, K.A., Refsum, H., Sutton, L. & Ueland, P.M. (1998) Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch. Neurol. 55, 14491455.
  • 5
    Miller, J.W. (1999) Homocysteine and Alzheimer's disease. Nutr. Rev. 57, 126129.
  • 6
    Blandini, F., Fancellu, R., Martignoni, E., Mangiagalli, A., Pacchetti, C., Samuele, A. & Nappi, G. (2001) Plasma homocysteine and l-DOPA metabolism in patients with Parkinson disease. Clin. Chem. 47, 11021104.
  • 7
    Duan, W., Ladenheim, B., Cutler, R.G., Kruman, I.I., Cadet, J.L. & Mattson, M.P. (2002) Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J. Neurochem. 80, 101110.
  • 8
    Kuhn, W., Roebroek, R., van Oppenraaij, D., Przuntek, H., Kretschmer, A., Buttner, T., Woitalla, D. & Muller, T. (1998) Elevated plasma levels of homocysteine in Parkinson's disease. Eur. Neurol. 40, 225227.
  • 9
    Yasui, K., Kowa, H., Nakaso, K., Takeshima, T. & Nakashima, K. (2000) Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with PD. Neurology 55, 437440.
  • 10
    Mattson, M.P. & Shea, T.B. (2003) Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends. Neurosci. 26, 137146.
  • 11
    Jacob, R.A., Gretz, D.M., Taylor, P.C., James, S.J., Pogribny, I.P., Miller, B.J., Henning, S.M. & Swendseid, M.E. (1998) Moderate folate depletion increases plasma homocysteine and decrease lymphocyte DNA methylation in postmenopausal women. J. Nutr. 128, 12041212.
  • 12
    Brattstrom, L., Israelsson, B., Lindgarde, F. & Hultberg, B. (1988) Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-syntase deficiency. Metabolism 37, 175178.
  • 13
    Siri, P.W., Verhoef, P. & Kok, F.J. (1998) Vitamins B6, B12, and folate: association with plasma total homocysteine and risk of coronary atherosclerosis. J. Am. Coll. Nutr. 17, 435441.
  • 14
    Frosst, P., Blom, H.J., Milos, R., Goyette, P., Sheppard, C.A., Matthews, R.G., Boers, G.J., den Heijer, M., Kluijtmans, L.A., van den Heuvel, L.P. et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat. Genet. 10, 111113.
  • 15
    Mudd, S.H., Finkelstein, J.D., Irreverre, F. & Laster, L. (1964) Homocystinuria: an enzymatic defect. Science 143, 14331445.
  • 16
    Abdelfatah, A., Ducloux, D., Toubin, G., Motte, G., Alber, D. & Chalopin, J.M. (2002) Treatment oh hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients. Transplantation 73, 663665.
  • 17
    Loscalzo, J. (1996) The oxidant stress of hyperhomocisteinemia. J. Clin. Invest. 98, 57.
  • 18
    Mujumdar, V.S., Aru, G.M. & Tyagi, S.C. (2001) Induction of oxidative stress by homocysteine impairs endothelial function. J. Cell. Biochem. 82, 491500.
  • 19
    Olszewski, A.J. & McCully, K.S. (1993) Homocysteine metabolism and the oxidative modification of proteins and lipids. Free Radic. Biol. Med. 14, 683693.
  • 20
    Bessede, G., Miguet, C., Gambert, P., Neel, D. & Lizard, G. (2001) Efficiency of homocysteine plus copper in inducing apoptosis is inversely proportional to gamma-glutamyl transpeptidase activity. FASEB J. 15, 19271940.
  • 21
    Kruman, I.I., Culmsee, C., Chan, S.L., Kruman, Y., Guo, Z., Penix, L. & Mattson, M.P. (2000) Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitoxicity. J. Neurosci. 20, 69206926.
  • 22
    Buttke, T.M. & Sandstrom, P.A. (1994) Oxidative stress as a mediator of apoptosis. Immunol. Today 15, 710.
  • 23
    Eckert, A., Cotman, C.W., Zerfass, R., Hennerici, M. & Muller, W.E. (1998) Lymphocytes as cell model to study apoptosis in Alzheimer's disease: vulnerability to programmed cell death appears to be altered. J. Neural. Transm. (Suppl) 54, 259267.
  • 24
    Gackowski, D., Kruszewski, M., Jawien, A., Ciecierski, M. & Olinski, R. (2001) Further evidence that oxidative stress may be a risk factor responsible for the development of atherosclerosis. Free Rad Res. 31, 542547.
  • 25
    Sandhu, S.K. & Kaur, G. (2002) Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes. Biogerontology 3, 161173.
  • 26
    Migliore, L., Petrozzi, L., Lucetti, C., Gambaccini, G., Bernardini, S., Scarpato, R., Trippi, F., Barale, R., Frenzilli, G., Rodilla, V. & Bonucelli, U. (2002) Oxidative damage and cytogenetic analysis in leukocytes of Parkinson's disease patients. Neurology 58, 18091815.
  • 27
    Zhang, Q., Zeng, X., Guo, J. & Wang, X. (2001) Effects of homocysteine on murine splenic B lymphocyte proliferation and its signal trasduction mechanism. Cardiovasc. Res. 52, 328336.
  • 28
    Park, J.R. & Hockenbery, D.M. (1996) Bcl-2, a novel regulator of apoptosis. J. Cell. Biochem. 60, 1217.
  • 29
    Sun, X.M., MacFarlane, M., Zhuang, J., Wolf, B.B., Green, D.R. & Cohen, G.M. (1999) Distinct caspase cascades are initiated in receptor-mediated and chemical-induced apoptosis. J. Biol. Chem. 274, 50535060.
  • 30
    Lincz, L.F. (1998) Deciphering the apoptotic pathway: all roads lead to death. Immunol. Cell. Biol. 76, 119.
  • 31
    Thornberry, N.A. & Lazebnik, Y. (1998) Caspase: enemies within. Science 281, 13121316.
  • 32
    Plantin-Carrenard, E., Bringuier, A., Derappe, C., Pichon, J., Guillot, R., Bernard, M., Foglietti, M.J., Feldmann, G., Aubery, M. & Braut-Boucher, F. (2003) A fluorescence microplate assay using yopro-1 to measure apoptosis: application to HL60 cells subjected to oxidative stress. Cell Biol. Toxicol. 19, 121133.
  • 33
    Long, L.H. & Halliwell, B. (2001) Oxidation and Generation of Hydrogen Peroxide by Thiol Compounds in Commonly Used Cell Culture Media. Biochem. Biophys. Res. Comm. 286, 991994.
  • 34
    Esterbauer, H. & Schaur, R.J. (1991) Zollner, H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free. Radic. Biol. Med. 11, 81128.
  • 35
    Frankfurt, O.S. & Krishan, A. (2001) Identification of apoptotic cells by formamide-induced DNA denaturation in condensed chromatin. J. Histochem. Cytochem. 49, 369378.
  • 36
    Frankfurt, O.S., Robb, J.A. & Sugarbaker, E.V. (1996) Villa, L. Monoclonal antibody to single-stranded DNA is a specific and sensitive cellular marker of apoptosis. Exp. Cell. Res. 226, 387397.
  • 37
    Charriaut-Marlangue, C. & Ben-Ari, Y. (1995) A cautionary note on the use of the TUNEL stain to determine apoptosis. Neuroreport 7, 6164.
  • 38
    Frankfurt, O.S. & Krishan, A. (2001) Enzyme-linked immunosorbent assay (ELISA) for the specific detection of apoptotic cells and its application to rapid drug screening. J. Immunol. Methods 253, 133144.
  • 39
    Zhang, C., Cai, Y., Adachi, M.T., Oshiro, S., Aso, T., Kaufman, R.J. & Kitajima, S. (2001) Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J. Biol. Chem. 276, 3586735874.
  • 40
    Hernanz, A., Fernandez-Vivancos, E., Montiel, C., Vazquez, J.J. & Arnalich, F. (2000) Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci. 67, 13171324.
  • 41
    Muniz, P., Saez, P., Iradi, A., Vina, J., Oliva, M.R. & Saez, G.T. (2001) Differences between cysteine and homocysteine in the induction of deoxyribose degradation and DNA damage. Free Radic. Biol. Med. 30, 354362.
  • 42
    Chen, P., Poddar, R., Tipa, E.V., Dibello, P.M., Moravec, C.D., Robinson, K., Green, R., Kruger, W.D., Garrow, T.A. & Jacobsen, D.W. (1999) Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocisteinemia and cardiovascular disease. Adv. Enzyme Regul. 39, 93109.
  • 43
    Moghadasian, M.H., McManus, B.M. & Frohlich, J.J. (1997) Homocyst(e)ine and coronary artery disease: clinical evidence and genetic and metabolic background. Arch. Intern. Med. 157, 22992308.
  • 44
    Zhang, Q., Zeng, X., Guo, J. & Wang, X. (2002) Oxidant stress mechanism of homocysteine potentiating ConA-induced proliferation in murine splenic T lymphocytes. Cardiovasc. Res. 53, 10351042.
  • 45
    Fenech, M. (1999) Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat. Res. 428, 299304.
  • 46
    Chambers, J.C., Ueland, P.M., Wright, M., Doré, C.J., Refsum, H. & Kooner, J.S. (2001) Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects. Circ. Res. 89, 187192.
  • 47
    Mansoor, M.A., Bergmark, C., Svardal, A.M., Lonning, P.E. & Ueland, P.M. (1995) Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and vascular disease. Arterioscler Thromb. Vasc. Biol. 15, 232240.
  • 48
    Ueland, P.M., Mansoor, M.A., Guttormsen, A.B., Muller, F., Aukrust, P., Refsum, H. & Svardal, A.M. (1996) Reduced, oxidized and protein-bound forms of homocysteine and other aminothiols in plasma comprise the redox thiol status – a possible element of extracellular antioxidant defense system. J. Nutr. 126, 1281S4S.
  • 49
    Zappacosta, B., Mordente, A., Persichilli, S., Minucci, A., Carlino, P., Martorana, G.E., Giardina, B. & De Sole, P. (2001) Is Homocisteine a Pro-oxidant? Free Rad Res. 35, 499505.
  • 50
    Jacobsen, D.W. (1998) Homocysteine and vitamins in cardiovascular disease. Clin. Chem. 44, 18331843.
  • 51
    Heinecke, J.W., Kawamura, M., Suzuki, L. & Chait, A. (1993) Oxidation of low density lipoprotein by thiols: superoxide-dependent and – independent mechanisms. J. Lipid Res. 34, 20512061.
  • 52
    Starkerbaum, G. & Harlan, J.M. (1986) Endothelial cell injury due copper-catalyzed hydrogen peroxide generation from homocysteine. J. Clin. Invest. 98, 57.
  • 53
    Sengupta, S., Chen, H., Togawa, T., DiBello, P.M., Majors, A.K., Budy, B., Ketterer, M.E. & Jacobsen, D.W. (2001) Albumin thiolate anion is an intermediate in the formation of albumin-S-S-homocysteine. J. Biol. Chem. 276, 3011130117.
  • 54
    Sengupta, S., Wehbe, C., Majors, A.K., Ketterer, M.E., Di Bello, P.M. & Jacobsen, D.W. (2001) Relative roles of albumin and ceruloplasmin in the formation of homocystine, homocysteine-cysteine-mixed disulfide, and cystine in the circulation. J. Biol. Chem. 276, 4689646904.
  • 55
    Ferrari, R., Ceconi, C., Curello, S., Cargnoni, A., Alfieri, O., Pardini, A., Marzollo, P. & Visioli, O. (1991) Oxygen free radicals and myocardial damage: protective role of thiol-containing agents. Am. J. Med. 91, 95S105S.
  • 56
    Cavalca, V., Cighetti, G., Bomonti, F., Loaldi, A., Bortone, L., Novembrino, C., De Franceschi, M., Belardinelli, R. & Guazzi, M.D. (2001) Oxidative stress and homocysteine in coronary artery disease. Clin. Chem. 47, 887892.
  • 57
    Dudman, N.P.B. (1999) An alternative view of homocysteine. Lancet 354, 20722074.
  • 58
    Chambers, J.C. & Kooner, J.S. (2001) Homocysteine: an innocent bystander in vascular disease? Eur. Heart J. 22, 717799.
  • 59
    Guilland, J.C., Favier, A., Potier de Courcy, G., Galan, P. & Hercberg, S. (2003) Hyperhomocysteinemia: an indipendent risk factor or a simple marker of vascular disease? Pathol. Biol. 51, 101110.