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-glutamyl transpeptidase activity
Inserm U498 (Métabolisme des lipoprotéines humaines et interactions vasculaires), CHU/Hôpital du Bocage, 21034 Dijon Cedex, France
1Correspondence: CHU/Hôpital du Bocage, Inserm U498, Laboratoire de Biochimie Médicale, BP 1542, 2 Bd Maréchal de Lattre de Tassigny, 21034 Dijon Cedex, France. E-mail: Gerard.Lizard{at}u-bourgogne.fr
Hyperhomocysteinemia represents an independent risk factor for
atherosclerosis, but the mechanisms leading to cellular dysfunctions
remain unknown. Using ECV304 cells, we found that homocysteine (Hcy)
plus copper (Cu2+) induced cytotoxic effects: loss of cell
adhesion, increased permeability to PI, and the occurrence of
morphologically apoptotic cells. This form of apoptosis, inhibited by
Z-VAD-fmk, was associated with a loss of mitochondrial potential, a
cytosolic release of cytochrome c, activation of
caspase-3, degradation of poly(ADP-ribose)polymerase, and
internucleosomal DNA fragmentation. However, the ability of Hcy plus
Cu2+ to induce apoptosis decreased when the pretreatment
culture time increased. As a positive correlation was found between the
length of time of culture before treatment and the enhancement of
-glutamyl transpeptidase (
-GT) activity, we asked whether
-GT
was involved in the control of Hcy plus Cu2+-induced
apoptosis. Therefore, ECV304 cells were treated with either acivicin or
dexamethasone, inhibiting and stimulating
-GT, respectively. In
ECV304 cells and human umbilical venous endothelial cells, acivicin
favored Hcy plus Cu2+-induced apoptosis whereas
dexamethasone counteracted the apoptotic process. As acivicin and
dexamethasone were also capable of modulating cell death in ECV304
cells treated with antitumoral drugs, our data emphasize that the
involvement of
-GT in the control of apoptosis is not restricted to
Hcy but also concerns other chemical compounds.Bessede,
G., Miguet, C., Gambert, P., Neel, D., Lizard, G. Efficiency of
homocysteine plus copper in inducing apoptosis is inversely
proportional to
-glutamyl transpeptidase activity.
Key Words: HUVECs ECV304 cells Hcy
-GT
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