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Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma

Year 2010, Volume: 23 Issue: 3, 249 - 253, 12.08.2010

Abstract

ABSTRACT

One of the main objective of the present study was to determine if erythrocytes play a role in regulation of plasma homocysteine concentration. Another objective was to investigate if erythrocytes convert homocystine into homocysteine. In the present study, we exposed erytrocytes to different concentrations of homocysteine and then measured the nonprotein sulfhydryl (NPSH) concentrations. Erythrocytes treated in the same manner were later utilized for the homocysteine efflux studies. The effect of temperature on the influx and the efflux processes were also evaluated. We also determined the rate of homocysteine influx in the presence of different amino acids. The homocysteine influx studies demonstrated that erythrocytes can respond to increases in homocysteine concentration in the extracellular media and influx homocysteine in a concentration-dependent manner. NPSH concentrations in erythrocytes treated with 1 mM homocysteine reached to 1.47 ï½± 0.01 ìmol/ml erythrocyte in 1 h whereas this concentration reached to 2.01 ï½± 0.1 ìmol/ml erythrocyte in 3 mM homocysteine treated erytrocytes. The homocysteine efflux is also determined to be time-and concentration -dependent. Extracellular concentration of NPSH in 1 mM homocysteine pre-treated erythrocytes reached to 0.266 ï½±  0.02 ìmol/ml erythrocyte in 1 h whereas this concentration reached to 0.64 ï½± 0.01 ìmol/ml erythrocyte with 3 mM homocysteine pre-treated erythrocytes. Our results also indicate that erythrocytes convert extracellulary applied homocystine into homocysteine. Depending on our results, it could be concluded that eryhtrocytes may play a significant role in the regulation of plasma homocysteine homeostasis.

References

  • 1] Eikelboom, J.W., Lonn, E., Genest, J., Hankey, G., Yusuf S., “Homocyst(e)ine and cardiovascular disease: a critical review of the
  • epidemiologic evidence”, Ann. Intern. Med., 131:363-375 (1999).
  • [2] Miller, A.L., Kelly, G.S., “Methionine and homocysteine metabolism and the nutritional prevention of ceratin birth defects and complications of pregnancy”, Alt. Med. Rev., 1 (4): 220-235 (1996).
  • [3] Medina, M.A., Urdiales, J.L., Sanchez, M.I.A., “Roles of homocysteine in cell metabolism.” Eu. J. Biochem., 268:3871-3882 (2001).
  • [4] Friedman, A.N., Bosto, A.G., Selhub, J., Levey, A.S., Rosenberg, I.H., “The kidney and homocysteine metabolism.” J. Am. Soc. Nephrol., 12:2181-2189 (2001).
  • [5] Finkelstein, J.D., “Methionine metabolism in mammals”. J. Nutr. Biochem., 1: 228-237 (1990).
  • [6] Ueland, P.M., Refsum, H., Stabler, S.P., Malinow, M.R., Andersson, A., Allen, R.H., “Total homocysteine in plasma or serum: methods and clinical applications.” Clin. Chem., 39:1764- 1779 (1993).
  • [7] Mayer, E.L., Jacobsen, D.W., Robinson, K., “Homocysteine and coronary atherosclerosis.” J. Am. Coll. Cardiol., 27: 517-527 (1996).
  • [8] Green, R., Jacobsen, D.W., “Clinical implications of hyperhomocysteinemia.” In: Bailey L.B., ed. Folate in health and disease. New York: Marcel Dekker Inc., 75-122, (1995).
  • [9] Mansoor, M.A., Ueland, P.M., Aarsland, A., Svardal, A.M. “Redox status and protein binding of plasma homocysteine and other aminothiols in patients with homocystinuria”, Metabolis. 42:1481-1485 (1993).
  • [10] Jacobsen, D.W., “Homocysteine and vitamines in cardiovascular disease.” Clin. Chem., 44 (8): 1833-1843 (1998).
  • [11] Coffey, M., Crowder, G..K., Cheek, D.J. “Reducing coronary artery disease by decreasing homocysteine levels.” Cirt. Care. Nurse., 23: 25-30 (2003).
  • [12] McCully, K.S., Wilson, R.B., “Homocysteine theory of atherosclerosis”, Atherosclerosis, 22: 215-227 (1975).
  • [13] Chambers, J.C., McGregor, A., Jean-Maria, J., Obeid, O.A., Kooner, J.S., “Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy.” Circulation, 99: 1156-1160 (1999).
  • [14] Kanani, P.M., Sinkey, C.A., Browning, R.L., Allaman, M., Knapp, H.R., Haynes, W.G., “Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocysteinemia in humans.” Circulation, 100: 1161-1168 (1999).
  • [15] Nappo, F., DeRosa, N., Marfella, R., DeLucia, D., Ingrosso, D., Perna, A.F., Farzati, B., Giugliano, D., “Impairement of endothelial dysfunctions by acute hyperhomocysteinemia and reversal by antioxidant vitamins”, JAMA, 281: 2113–2118 (1999).
  • [16] Starkebaum, G., Harlan, J.M., “Endothelial cell injury due to copper catalyzed hydrogen peroxide generation from homocysteine”, J. Clin. Invest., 77: 1370-1376 (1986).
  • [17] Misra, H.P., “Generation of superoxide free radical during the autooxidation of thiols”, J. Biol. Chem., 249: 2151-2155 (1974).
  • [18] Awasthi, Y. C., Mısra, G., Rassın, D. K., Srivastava, S. K., “Detoxification of xenobiotics by glutathione S-transferase in erythrocytes: the transport of the conjugate of glutathione and 1- chloro-2,4-dinitrobenzene”, Brit. J. Haematol., 55:419-425 (1983).
  • [19] Sedlak, J., Lindsay, R. H., “Determination of sulfhydriyl groups in biological samples.” Anal. Biochem, 25: 192-205 (1963).
  • [20] Jiang, X., Yang, F., Brailoiu, E., Jakubowski, H., Dun, N.J., Schafer, A.I., Yang, X., Durante, W., Wang, H., “Differential Regulation of Homocysteine Transport in Vascular Endothelial and Smooth Muscle Cells”, Arterioscl.Throm. Vas., 27:1976-1982 (2007).
  • [21] Verhoef, P., Van, Vliet, T., Olthof, M.R., Katan, M.B., “A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers”, Am. J. Clin. Nutr., 82 (3):553- 558 (2005).
  • [22] Ragone, R., “Homocystine solubility and vascular disease”, The FASEB J., 16:401-404 (2002).
  • [23] Eldjarn, L., Bremer, J., Borresen, C., “The reduction of disulfides by human erythrocytes”, Biochem. J., 82:192-197 (1962).
  • [24] Reglinski, J., Hoey, S., Smith, W.E., Sturrock, R.D., “Cellular response to oxidative stress at sulfhydryl group receptor sites on the erythrocyte membrane”, J. Biol. Chem., 263 (25):12360-12366 (1988).
  • [25] Ciriolo, M.R., Paci, M., Sette, M., De Martino, A., Bozzi, A., Rotilio, G., “Transduction of reducing power across the plasma membrane by reduced glutathione. A 1H-NMR spin-echo study of intact human erythrocytes”, Eur. J. Biochem., 215(3): 711- 718 (1993)
Year 2010, Volume: 23 Issue: 3, 249 - 253, 12.08.2010

Abstract

References

  • 1] Eikelboom, J.W., Lonn, E., Genest, J., Hankey, G., Yusuf S., “Homocyst(e)ine and cardiovascular disease: a critical review of the
  • epidemiologic evidence”, Ann. Intern. Med., 131:363-375 (1999).
  • [2] Miller, A.L., Kelly, G.S., “Methionine and homocysteine metabolism and the nutritional prevention of ceratin birth defects and complications of pregnancy”, Alt. Med. Rev., 1 (4): 220-235 (1996).
  • [3] Medina, M.A., Urdiales, J.L., Sanchez, M.I.A., “Roles of homocysteine in cell metabolism.” Eu. J. Biochem., 268:3871-3882 (2001).
  • [4] Friedman, A.N., Bosto, A.G., Selhub, J., Levey, A.S., Rosenberg, I.H., “The kidney and homocysteine metabolism.” J. Am. Soc. Nephrol., 12:2181-2189 (2001).
  • [5] Finkelstein, J.D., “Methionine metabolism in mammals”. J. Nutr. Biochem., 1: 228-237 (1990).
  • [6] Ueland, P.M., Refsum, H., Stabler, S.P., Malinow, M.R., Andersson, A., Allen, R.H., “Total homocysteine in plasma or serum: methods and clinical applications.” Clin. Chem., 39:1764- 1779 (1993).
  • [7] Mayer, E.L., Jacobsen, D.W., Robinson, K., “Homocysteine and coronary atherosclerosis.” J. Am. Coll. Cardiol., 27: 517-527 (1996).
  • [8] Green, R., Jacobsen, D.W., “Clinical implications of hyperhomocysteinemia.” In: Bailey L.B., ed. Folate in health and disease. New York: Marcel Dekker Inc., 75-122, (1995).
  • [9] Mansoor, M.A., Ueland, P.M., Aarsland, A., Svardal, A.M. “Redox status and protein binding of plasma homocysteine and other aminothiols in patients with homocystinuria”, Metabolis. 42:1481-1485 (1993).
  • [10] Jacobsen, D.W., “Homocysteine and vitamines in cardiovascular disease.” Clin. Chem., 44 (8): 1833-1843 (1998).
  • [11] Coffey, M., Crowder, G..K., Cheek, D.J. “Reducing coronary artery disease by decreasing homocysteine levels.” Cirt. Care. Nurse., 23: 25-30 (2003).
  • [12] McCully, K.S., Wilson, R.B., “Homocysteine theory of atherosclerosis”, Atherosclerosis, 22: 215-227 (1975).
  • [13] Chambers, J.C., McGregor, A., Jean-Maria, J., Obeid, O.A., Kooner, J.S., “Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy.” Circulation, 99: 1156-1160 (1999).
  • [14] Kanani, P.M., Sinkey, C.A., Browning, R.L., Allaman, M., Knapp, H.R., Haynes, W.G., “Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocysteinemia in humans.” Circulation, 100: 1161-1168 (1999).
  • [15] Nappo, F., DeRosa, N., Marfella, R., DeLucia, D., Ingrosso, D., Perna, A.F., Farzati, B., Giugliano, D., “Impairement of endothelial dysfunctions by acute hyperhomocysteinemia and reversal by antioxidant vitamins”, JAMA, 281: 2113–2118 (1999).
  • [16] Starkebaum, G., Harlan, J.M., “Endothelial cell injury due to copper catalyzed hydrogen peroxide generation from homocysteine”, J. Clin. Invest., 77: 1370-1376 (1986).
  • [17] Misra, H.P., “Generation of superoxide free radical during the autooxidation of thiols”, J. Biol. Chem., 249: 2151-2155 (1974).
  • [18] Awasthi, Y. C., Mısra, G., Rassın, D. K., Srivastava, S. K., “Detoxification of xenobiotics by glutathione S-transferase in erythrocytes: the transport of the conjugate of glutathione and 1- chloro-2,4-dinitrobenzene”, Brit. J. Haematol., 55:419-425 (1983).
  • [19] Sedlak, J., Lindsay, R. H., “Determination of sulfhydriyl groups in biological samples.” Anal. Biochem, 25: 192-205 (1963).
  • [20] Jiang, X., Yang, F., Brailoiu, E., Jakubowski, H., Dun, N.J., Schafer, A.I., Yang, X., Durante, W., Wang, H., “Differential Regulation of Homocysteine Transport in Vascular Endothelial and Smooth Muscle Cells”, Arterioscl.Throm. Vas., 27:1976-1982 (2007).
  • [21] Verhoef, P., Van, Vliet, T., Olthof, M.R., Katan, M.B., “A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers”, Am. J. Clin. Nutr., 82 (3):553- 558 (2005).
  • [22] Ragone, R., “Homocystine solubility and vascular disease”, The FASEB J., 16:401-404 (2002).
  • [23] Eldjarn, L., Bremer, J., Borresen, C., “The reduction of disulfides by human erythrocytes”, Biochem. J., 82:192-197 (1962).
  • [24] Reglinski, J., Hoey, S., Smith, W.E., Sturrock, R.D., “Cellular response to oxidative stress at sulfhydryl group receptor sites on the erythrocyte membrane”, J. Biol. Chem., 263 (25):12360-12366 (1988).
  • [25] Ciriolo, M.R., Paci, M., Sette, M., De Martino, A., Bozzi, A., Rotilio, G., “Transduction of reducing power across the plasma membrane by reduced glutathione. A 1H-NMR spin-echo study of intact human erythrocytes”, Eur. J. Biochem., 215(3): 711- 718 (1993)
There are 26 citations in total.

Details

Primary Language English
Journal Section Biology
Authors

Deniz Yıldız This is me

Züleyha Çivi This is me

Zuleyha Cıvı This is me

Yeliz Çakır This is me

Publication Date August 12, 2010
Published in Issue Year 2010 Volume: 23 Issue: 3

Cite

APA Yıldız, D., Çivi, Z., Cıvı, Z., Çakır, Y. (2010). Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma. Gazi University Journal of Science, 23(3), 249-253.
AMA Yıldız D, Çivi Z, Cıvı Z, Çakır Y. Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma. Gazi University Journal of Science. September 2010;23(3):249-253.
Chicago Yıldız, Deniz, Züleyha Çivi, Zuleyha Cıvı, and Yeliz Çakır. “Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma”. Gazi University Journal of Science 23, no. 3 (September 2010): 249-53.
EndNote Yıldız D, Çivi Z, Cıvı Z, Çakır Y (September 1, 2010) Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma. Gazi University Journal of Science 23 3 249–253.
IEEE D. Yıldız, Z. Çivi, Z. Cıvı, and Y. Çakır, “Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma”, Gazi University Journal of Science, vol. 23, no. 3, pp. 249–253, 2010.
ISNAD Yıldız, Deniz et al. “Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma”. Gazi University Journal of Science 23/3 (September 2010), 249-253.
JAMA Yıldız D, Çivi Z, Cıvı Z, Çakır Y. Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma. Gazi University Journal of Science. 2010;23:249–253.
MLA Yıldız, Deniz et al. “Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma”. Gazi University Journal of Science, vol. 23, no. 3, 2010, pp. 249-53.
Vancouver Yıldız D, Çivi Z, Cıvı Z, Çakır Y. Homocysteine Influx and Efflux: Participation of Erythrocytes in Homocysteine Homeostasis of the Plasma. Gazi University Journal of Science. 2010;23(3):249-53.