Oxidative Stress Activated by Keap-1/Nrf2 Signaling Pathway in Pathogenesis of Preeclampsia

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2020 Apr 10

PMID 32269675

Citations 11

Authors

Hao Feng

Li Wang

Guoxiang Zhang

Zhiwei Zhang

Wei Guo

Affiliations

Soon will be listed here.

Abstract

We aimed to investigate the effect of Keap1/Nrf2 pathway on the biologic function of trophoblast cells in the oxidative stress model at the cellular level, and analyze the expression levels and clinical significance of Keap1/Nrf2 related antioxidant factors in placental tissues of preeclampsia (PE) patients at clinical level. In this study, we found that under hypoxia/reoxygenation conditions, the activities of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in HTR8/SVneo cells were significantly lower than those before treatment (P<0.01). The activities of CAT, GSH-Px and SOD in HTR8/SVneo cells in siRNA+H/R group decreased significantly (P<0.01), which indicated the important defensive effect of Keap1/Nrf2 pathway in oxidative stress. Compared with Nrf2 siRNA+H/R group, Si-NC+H/R group had CAT, GSH-Px and SOD activities decreasing, which were similar to those in the H/R group. Moreover, the activities of oxidative stress-related active enzymes in patients with preeclampsia were further confirmed by detecting and comparing the activities of CAT, GSH-Px and SOD in placental tissues. The results showed that the activities of SOD (P<0.001), GSH-Px (P<0.01) and CAT (P<0.01) in placental tissues of patients with PE were significant different from those of normal placental tissues. The expression level of Keap1 in placenta of patients with PE was slightly lower than that of normal placenta, while the expression of Nrf2 and HO-1 in placenta of patients with PE were significantly higher than those of normal placenta, which implicated the importance of Keap-1/Nrf2 pathway in PE.

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References

Than N, Romero R, Tarca A, Kekesi K, Xu Y, Xu Z . Integrated Systems Biology Approach Identifies Novel Maternal and Placental Pathways of Preeclampsia. Front Immunol. 2018; 9:1661. PMC: 6092567. DOI: 10.3389/fimmu.2018.01661. View

Lu M, Ji J, Jiang Z, You Q . The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update. Med Res Rev. 2016; 36(5):924-63. DOI: 10.1002/med.21396. View

Jauniaux E, Burton G . [The role of oxidative stress in placental-related diseases of pregnancy]. J Gynecol Obstet Biol Reprod (Paris). 2016; 45(8):775-785. DOI: 10.1016/j.jgyn.2016.02.012. View

Farajian-Mashhadi F, Eskandari F, Rezaei M, Eskandari F, Najafi D, Teimoori B . The possible role of maternal and placental polymorphisms and haplotypes in pathogenesis of preeclampsia. Clin Exp Hypertens. 2019; 42(2):171-176. DOI: 10.1080/10641963.2019.1601203. View

Correa P, Palmeiro Y, Soto M, Ugarte C, Illanes S . Etiopathogenesis, prediction, and prevention of preeclampsia. Hypertens Pregnancy. 2016; 35(3):280-94. DOI: 10.1080/10641955.2016.1181180. View

Menon R . Oxidative stress damage as a detrimental factor in preterm birth pathology. Front Immunol. 2014; 5:567. PMC: 4228920. DOI: 10.3389/fimmu.2014.00567. View

Wang J, Jiang C, Zhang K, Lan X, Chen X, Zang W . Melatonin receptor activation provides cerebral protection after traumatic brain injury by mitigating oxidative stress and inflammation via the Nrf2 signaling pathway. Free Radic Biol Med. 2018; 131:345-355. DOI: 10.1016/j.freeradbiomed.2018.12.014. View

Martin L, Moco N, Lima M, Polettini J, Miot H, Correa C . Histologic chorioamnionitis does not modulate the oxidative stress and antioxidant status in pregnancies complicated by spontaneous preterm delivery. BMC Pregnancy Childbirth. 2017; 17(1):376. PMC: 5684743. DOI: 10.1186/s12884-017-1549-4. View

OGorman N, Wright D, Poon L, Rolnik D, Syngelaki A, De Alvarado M . Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations. Ultrasound Obstet Gynecol. 2017; 49(6):756-760. DOI: 10.1002/uog.17455. View

10.

Dutta E, Behnia F, Boldogh I, Saade G, Taylor B, Kacerovsky M . Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes. Mol Hum Reprod. 2015; 22(2):143-57. DOI: 10.1093/molehr/gav074. View

11.

Ci X, Lv H, Wang L, Wang X, Peng L, Qin F . The antioxidative potential of farrerol occurs via the activation of Nrf2 mediated HO-1 signaling in RAW 264.7 cells. Chem Biol Interact. 2015; 239:192-9. DOI: 10.1016/j.cbi.2015.06.032. View

12.

Masoura S, Makedou K, Theodoridis T, Kourtis A, Zepiridis L, Athanasiadis A . The involvement of uric acid in the pathogenesis of preeclampsia. Curr Hypertens Rev. 2015; 11(2):110-5. DOI: 10.2174/1573402111666150529130703. View

13.

Chasan-Taber L . Physical activity and dietary behaviors associated with weight gain and impaired glucose tolerance among pregnant Latinas. Adv Nutr. 2012; 3(1):108-18. PMC: 3262610. DOI: 10.3945/an.111.001214. View

14.

Goulopoulou S, Davidge S . Molecular mechanisms of maternal vascular dysfunction in preeclampsia. Trends Mol Med. 2014; 21(2):88-97. DOI: 10.1016/j.molmed.2014.11.009. View

15.

Mosimann B, Pfiffner C, Amylidi-Mohr S, Risch L, Surbek D, Raio L . First trimester combined screening for preeclampsia and small for gestational age - a single centre experience and validation of the FMF screening algorithm. Swiss Med Wkly. 2017; 147:w14498. DOI: 10.4414/smw.2017.14498. View

16.

Lv X, Li X, Dai X, Liu M, Wu C, Song W . Investigation polymorphism with the pathogenesis of preeclampsia. Clin Exp Hypertens. 2019; 42(2):167-170. DOI: 10.1080/10641963.2019.1601202. View

17.

Lopez-Jaramillo P, Barajas J, Rueda-Quijano S, Lopez-Lopez C, Felix C . Obesity and Preeclampsia: Common Pathophysiological Mechanisms. Front Physiol. 2019; 9:1838. PMC: 6305943. DOI: 10.3389/fphys.2018.01838. View

18.

Sircar M, Thadhani R, Karumanchi S . Pathogenesis of preeclampsia. Curr Opin Nephrol Hypertens. 2015; 24(2):131-8. DOI: 10.1097/MNH.0000000000000105. View

19.

Tang C, Liang J, Qian J, Jin L, Du M, Li M . Opposing role of JNK-p38 kinase and ERK1/2 in hydrogen peroxide-induced oxidative damage of human trophoblast-like JEG-3 cells. Int J Clin Exp Pathol. 2014; 7(3):959-68. PMC: 3971298. View

20.

Masoumi Z, Maes G, Herten K, Cortes-Calabuig A, Alattar A, Hanson E . Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells. Int J Mol Sci. 2019; 20(8). PMC: 6514549. DOI: 10.3390/ijms20082038. View