Effect of endothelin‐1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells

European Journal of Clinical Investigation - Tập 32 Số 8 - Trang 556-562 - 2002
Fortunato Scalera1, Ralf Dittrich1, Matthias W. Beckmann1, Ernst Beinder1
1University of Erlangen - Nuremberg, Erlangen, Germany#TAB#

Tóm tắt

AbstractBackground The major pathophysiologic changes observed in preeclampsia suggest that endothelial cell dysfunction plays an important role in this disorder. The pathway mediating endothelial cell layer dysfunction is unknown. The concentration of endothelin‐1 (ET‐1), a potent mammalian vasoconstrictor peptide produced by the vascular endothelium, has been observed to be significantly increased in preeclampsia. In this study, we determined the in vitro effect of endothelin‐1 on glutathione and lipid peroxide levels and on the secretion of vasoactive substances by human umbilical vein endothelial cells (HUVECs).Methods Human umbilical vein endothelial cells were incubated for 24 h in the presence of different concentrations of ET‐1 (0–1000 pmol L−1), which were shown in an earlier experiment to have no effects on vitality and proliferation rate of HUVECs. The levels of glutathione (GSH) and lipid peroxides (LPO) were measured in endothelial cell lysates. For the measurement of vasoactive substances, levels of nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2 (TXA2) were measured in endothelial cell supernatants.Results At lower concentrations (5–50 pmol L−1), ET‐1 increases the intracellular content of LPO, stimulates the secretion of TXA2, but inhibits the secretion of PGI2 in endothelial cells compared with control cells. At higher concentrations (100–1000 pmol L−1), ET‐1 increases the intracellular content of GSH, but results in a decrease of LPO, and increase of PGI2, back to control levels. ET‐1 has no effect on NO secretion.Conclusion These findings demonstrate that at concentrations corresponding to values in plasma from preeclamptic women, ET‐1 induces oxidative stress and results in altered secretion of vasoactive substances in human endothelial cells. We conclude that ET‐1 may participate in the pathway leading to endothelial cell dysfunction seen in preeclampsia.

Từ khóa


Tài liệu tham khảo

10.1038/332411a0

10.1097/00004872-199816080-00001

Rubanyi GM, 1994, Endothelins. molecular biology, biochemistry, pharmacology physiology and pathophysiology, Pharmacol Rev, 46, 325

10.1210/jcem-71-6-1675

10.1097/00005344-199100177-00127

10.1016/0002-9378(91)90317-K

10.1016/0002-9378(93)90486-3

10.1016/0002-9378(93)90154-B

10.1016/S0029-7844(97)00093-8

10.1111/j.1471-0528.1998.tb09944.x

10.1136/fn.80.2.F123

Battistini B, 1993, Endothelins: circulating plasma levels and presence in other biologic fluids, Lab Invest, 68, 600

10.1161/01.HYP.30.6.1585

10.1016/0006-291X(92)92382-8

10.1111/j.1749-6632.1994.tb12035.x

10.1016/S0301-2115(01)00412-2

10.1016/0002-9378(89)90665-0

10.1016/S0095-5108(18)30490-1

10.1016/0002-9378(89)90778-3

Deneke SM, 1989, Regulation of cellular glutathione, Am J Physiol, 257, L163

10.1055/s-2007-1016254

10.1046/j.1525-1373.1999.d01-139.x

Morgan SJ, 1994, Kultur tierischer Zellen, 69

Chappell LC, 1994, Effect of antioxidants on the occurrence of pre‐eclampsia in women at increased risk: a radomised trial, Lancet, 354, 810, 10.1016/S0140-6736(99)80010-5

10.1001/jama.285.12.1607

10.1067/mob.2001.116754

10.1161/01.CIR.75.5.956

10.1016/S0272-6386(12)81117-6

10.1016/S0002-9378(12)80017-2

10.1006/bbrc.2000.2354

10.1016/S0890-6238(99)00033-7

McCay PB, 1989, B Glutathione: Chemical, Biochemical and Medical Aspects, 111

10.1007/BF01870891

Gray CA, 1995, Molecular Biology and Pharmacology of the Endothelins, 95

Warso MA, 1983, Lipid peroxidation in relation to prostacyclin and thromboxane physiology and pathophysiology, Br Med Bull, 39, 277, 10.1093/oxfordjournals.bmb.a071833

10.1016/0891-5849(89)90131-7

Beckmann JS, 1996, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly, Am J Physiol, 271, C1424, 10.1152/ajpcell.1996.271.5.C1424

10.3109/10641950109152641

Thông tin
Thông tin xuất bản

European Journal of Clinical Investigation

Tập 32 Số 8

556-562

Thông tin tác giả