PMID: 11606190Oct 19, 2001Paper

Homocysteine-induced decrease in endothelin-1 production is initiated at the extracellular level and involves oxidative products

European Journal of Biochemistry
Séverine DrunatKarine Demuth

Abstract

The increased cardiovascular risk associated with hyperhomocysteinemia has been partly related to homocysteine (Hcy)-induced endothelial cell dysfunction. However, the intra or extracellular starting point of the interaction between Hcy and endothelial cells, leading to cellular dysfunction, has not yet been identified. We investigated the effects of both intracellular and extracellular Hcy accumulation on endothelin-1 (ET-1) synthesis by cultured human endothelial cells. Incubation of cultures with methionine (1.0 mmol x L(-1)) for 2 h induced a slight increase in cellular Hcy content but no change in ET-1 production. Incubation of cells with Hcy (0.2 mmol x L(-1)) led to a significant fall in ET-1 generation, accompanied by a significant increase in cellular Hcy content. Addition of the amino-acid transport system L substrate 2-amino-2-norbornane carboxylic acid had no effect on the Hcy-induced decrease in ET-1 production but significantly inhibited the Hcy-induced increase in the cellular Hcy content. Incubation of cells with a lower Hcy concentration (0.05 mmol x L(-1)) also reduced ET-1 production without increasing the cellular Hcy content. Co-incubation with extracellular free-radical inhibitors (superoxide dismutase, ca...Continue Reading

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Citations

Feb 8, 2007·Amino Acids·J Perła-KajánH Jakubowski
Jan 25, 2008·Journal of Bioenergetics and Biomembranes·Javier Rodríguez-AlonsoMiguel Angel Medina
Mar 15, 2003·Clinica Chimica Acta; International Journal of Clinical Chemistry·Björn Hultberg
Sep 5, 2002·Free Radical Biology & Medicine·Séverine DrunatKarine Demuth
Nov 10, 2007·Clinical Chemistry and Laboratory Medicine : CCLM·Gian Paolo RossiAchille Cesare Pessina
Aug 21, 2007·Lancet Neurology·J David Spence
Feb 22, 2013·Cell Biology International·Magdalena P CortésIrene Quintana
May 23, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Vasiliki LikogianniKarine Demuth
May 21, 2016·Redox Report : Communications in Free Radical Research·Elena Díaz-SantiagoMiguel Ángel Medina
Apr 27, 2004·Journal of Cellular Biochemistry·Gianna FerrettiGiovanna Curatola
Sep 23, 2006·Clinical Chemistry·Angelo ZinelluCiriaco Carru
Jan 22, 2005·Journal of Hypertension·Hanspeter BrunnerUNKNOWN Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension
Aug 16, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Ayako YoshidaVictor M Elner

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