Study Of The Effect About Endothelin-1 On The Redox State In JEG-3 Cell

Object:Endothelin-1(ET-1) in preeclampsia pregnant women is elevated, research has demonstrated ET-1 can cause many kinds of tissue and cell oxidative stress damage.Our study investigates the effect about ET-1 on the redox state and the proliferative ability in trophoblast cell to reveal the mechanism about the elevated ET-1 in preeclampsia how to damage the trophoblast cell.Method:JEG-3 cell was treated with various concentration of ET-1(0,10,20,50,100及1000 pg/ml)for 6 and 24 hours respectively,then observing the markers of oxidative stress [malondialdehyde(MDA), glutathione(GSH),superoxide dismutase(SOD)] in JEG-3 cell as well as cell proliferation and vitality after stimulation periods.Meanwhile, observing the change of the index mentioned above after pretreated JEG-3 cell with the ETA receptor antagonist BQ123.Result:(1) ET-1(20～50 pg/ml)can significantly increase MDA in JEG-3 cell,while ET-1(50～100 pg/ml)significantly decreases its MDA,but stimulation for 24 hours,the value of MDA in JEG-3 cell corresponding the concentration of ET-1(50～100 pg/ml)is still higher than its value corresponding ET-1 (20 pg/ml)(P<0.001).Pretreated with BQ123 can significantly decrease MDA in JEG-3 cell.(2) ET-1(20～50 pg/ml)can significantly decrease GSH in JEG-3 cell,while ET-1(50～100 pg/ml)significantly increases its GSH,but stimulation for 24 hours,the value of GSH corresponding the concentration of ET-1( 100 pg/ml) is still significantly lower than its value corresponding ET-1 (10 pg/ml).(3) ET-1(20～50 pg/ml)can significantly increase SOD inhibition ratio in JEG-3 cell,while ET-1(50～100 pg/ml)significantly degrades its SOD inhibition ratio,but stimulation for 24 hours,the value of SOD inhibition ratio corresponding the concentration of ET-1(50～100 pg/ml)is still higher than its value corresponding ET-1 (20 pg/ml) ( P<0.05 ) .Pretreated with BQ123 can significantly degrade SOD inhibition ratio in JEG-3 cell.(4) ET-1(0～20 pg/ml)enhanced JEG-3 cell proliferation,while ET-1(20～1000 pg/ml)restraines the proliferation and vitality of trophoblast cell.Along with raising the concentration of ET-1,the proliferation ability of JEG-3 cell is gradually depressed. Especially for 24 hours stimulation periods,the proliferation of JEG-3 cell is sharply decreased after treated with endothelin-1(50～100 pg/ml).Conclusion:The concentration of ET-1(20～100 pg/ml) corresponding to its level in the circulation of preeclampsia pregnant women results in the significant lipid peroxidation reaction and weakenes the antioxidant ability in trophoblast cell, as well as decreases proliferation and vitality of trophoblast cell.Therefore,we presume ET-1 possibly paticipates in the pathogenesis of preeclampsia via oxidative stress damage and inhibiting the proliferation and vitality of trophoblast cell.