Comparative study on in vitro effects of homocysteine thiolactone and homocysteine on HUVEC cells: evidence for a stronger proapoptotic and proinflammative homocysteine thiolactone.
Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis. However the underlying mechanisms responsible for endothelial cell injury with increased plasma concentration of homocysteine or homocysteine derivatives remains still incompletely elucidated. In this study, we investigated the ability of homocysteine (Hcy) and homocysteine thiolactone (HcyT) to induce cell death and IL-8 secretion in primary human umbilical vein endothelial cells (HUVEC). Hcy and HcyT were both cytotoxic and capable of promoting cell death, as measured by caspase-3 activation and DNA fragmentation. ELISA assays clearly demonstrated that Hcy and HcyT strongly activated IL-8 release. Furthermore, our results showed that HcyT was much more efficient than Hcy in activating caspase-3 or in inducing IL-8 secretion. The use of antioxidants such as vitamin C and vitamin E strongly but not completely reduced programmed cell death and chemokine release suggesting that other pathways different than reactive oxygen species are also involved. This study suggests that Homocysteine derivatives like HcyT might possess stronger cytotoxicity and pro-inflammatory properties and that Hcy derivatives levels should therefore be more taken into account during diagnostics.
Kerkeni
Mohsen
M
Research Unit 03/UR/08-14, Faculty of Pharmacy, Monastir, Tunisia. m.kerkeni@belgique.com
Tnani
Mehdi
M
Chuniaud
Laurence
L
Miled
Abdelhedi
A
Maaroufi
Khira
K
Trivin
François
F
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D000975:Antioxidants; D018836:Inflammation Mediators; D016209:Interleukin-8; D006710:Homocysteine; C007957:homocysteine thiolactone; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3