Vitamin D Reduces Oxidative Stress-Induced Procaspase-3/ROCK1 Activation and MP Release by Placental Trophoblasts

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2017 Apr 4

PMID 28368445

Citations 11

Authors

Jie Xu

Xiuyue Jia

Yang Gu

David F Lewis

Xin Gu

Yuping Wang

Affiliations

Soon will be listed here.

Abstract

Context: Increased microparticle (MP) shedding by placental trophoblasts contributes to maternal vascular inflammatory response and endothelial dysfunction in preeclampsia. Vitamin D has beneficial effects in pregnancy; however, its effect on trophoblast MP release has not been investigated.

Objective: To investigate if vitamin D could protect trophoblasts from oxidative stress-induced MP release.

Design: Placental trophoblasts were isolated from uncomplicated and preeclamptic placentas. Effects of vitamin D on MP release induced by oxidative stress inducer CoCl2 were studied.

Main Outcome Measures: Annexin V+ MPs were assessed by flow cytometry. Expression of caveolin-1, endothelial nitric oxide synthase (eNOS), procaspase-3, cleaved caspase-3, and Rho-associated coiled-coil protein kinase 1 (ROCK1) in trophoblasts and trophoblast-derived MPs were determined by Western blot.

Results: Trophoblasts from preeclamptic pregnancies released significantly more MPs than cells from uncomplicated pregnancies (P < 0.01). CoCl2-induced increase in MP release was associated with upregulation of caveolin-1 and downregulation of eNOS expression in trophoblasts (P < 0.05), which could be attenuated by 1,25(OH)2D3. Moreover, 1,25(OH)2D3 could also inhibit CoCl2-induced procaspase-3 cleavage and ROCK1 activation in trophoblasts. Consistently, CoCl2-induced upregulation of procaspase-3, cleaved caspase-3, and ROCK1 expression in trophoblast-derived MPs were also reduced in cells treated with 1,25(OH)2D3.

Conclusions: Placental trophoblasts from preeclamptic pregnancies released more MP than cells from uncomplicated pregnancies. Oxidative stress-induced increase in MP shedding is associated with upregulation of caveolin-1 and downregulation of eNOS expression in placental trophoblasts. Inhibition of caspase-3 cleavage and ROCK1 activation, together with upregulation of eNOS expression, could be the potential cellular/molecular mechanism(s) of vitamin D protective effects on placental trophoblasts.

Citing Articles

Extracellular Vesicles as Biomarkers of Pregnancy Complications.

Popova A, Vashukova E, Illarionov R, Maltseva A, Pachuliia O, Postnikova T Int J Mol Sci. 2024; 25(22).

PMID: 39596014 PMC: 11594130. DOI: 10.3390/ijms252211944.

Inhibition of LAMP3 mediates the protective effect of vitamin D against hypoxia/reoxygenation in trophoblast cells.

Tian X, Zheng L, Ma J, Xu Y, Zhang Y, Pi Y Braz J Med Biol Res. 2023; 56:e12816.

PMID: 37878884 PMC: 10591490. DOI: 10.1590/1414-431X2023e12816.

Vitamin D stimulates placental L-type amino acid transporter 1 (LAT1) in preeclampsia.

Jia X, Cao Y, Ye L, Liu X, Huang Y, Yuan X Sci Rep. 2022; 12(1):4651.

PMID: 35301401 PMC: 8931068. DOI: 10.1038/s41598-022-08641-y.

Association between Maternal Serum 25-Hydroxyvitamin D Concentrations and the Risk of Preterm Birth in Central Sudan: A Case-Control Study.

Abdelrahiem S, Sharif M, AlHabardi N, Al-Wutayd O, Adam I Nutrients. 2022; 14(4).

PMID: 35215541 PMC: 8879935. DOI: 10.3390/nu14040891.

VIP Stabilizes the Cytoskeleton of Schlemm's Canal Endothelia via Reducing Caspase-3 Mediated ZO-1 Endolysosomal Degradation.

Lou X, Mou Q, Zhao B, Huang J, Yao K, Luo Z Oxid Med Cell Longev. 2021; 2021:9397960.

PMID: 34552687 PMC: 8452417. DOI: 10.1155/2021/9397960.

References

Goldberg M, Schneider T . Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem. 1994; 269(6):4355-9. View

Lee W, Choi J, Cha S . Co-localization and interaction of human organic anion transporter 4 with caveolin-1 in primary cultured human placental trophoblasts. Exp Mol Med. 2008; 40(5):505-13. PMC: 2679353. DOI: 10.3858/emm.2008.40.5.505. View

Jia X, Xu J, Gu Y, Gu X, Li W, Wang Y . Vitamin D suppresses oxidative stress-induced microparticle release by human umbilical vein endothelial cells. Biol Reprod. 2017; 96(1):199-210. PMC: 6025229. DOI: 10.1095/biolreprod.116.142604. View

Chen J, Zhan Y, Yang C, Tzeng S . Oxidative stress-induced attenuation of thrombospondin-1 expression in primary rat astrocytes. J Cell Biochem. 2010; 112(1):59-70. DOI: 10.1002/jcb.22732. View

Germain S, Sacks G, Sooranna S, Soorana S, Sargent I, Redman C . Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles. J Immunol. 2007; 178(9):5949-56. DOI: 10.4049/jimmunol.178.9.5949. View

Perez-Lopez F, Pasupuleti V, Mezones-Holguin E, Benites-Zapata V, Thota P, Deshpande A . Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril. 2015; 103(5):1278-88.e4. DOI: 10.1016/j.fertnstert.2015.02.019. View

Sun J, Zhong W, Gu Y, Groome L, Wang Y . 1,25(OH)2D3 suppresses COX-2 up-regulation and thromboxane production in placental trophoblast cells in response to hypoxic stimulation. Placenta. 2013; 35(2):143-5. PMC: 4017579. DOI: 10.1016/j.placenta.2013.12.002. View

Bhanushali A, Lajpal N, Kulkarni S, Chavan S, Bagadi S, Das B . Frequency of fokI and taqI polymorphism of vitamin D receptor gene in Indian population and its association with 25-hydroxyvitamin D levels. Indian J Hum Genet. 2010; 15(3):108-13. PMC: 2922626. DOI: 10.4103/0971-6866.60186. View

Haugen M, Brantsaeter A, Trogstad L, Alexander J, Roth C, Magnus P . Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009; 20(5):720-6. DOI: 10.1097/EDE.0b013e3181a70f08. View

10.

Ma R, Gu Y, Zhao S, Sun J, Groome L, Wang Y . Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am J Physiol Endocrinol Metab. 2012; 303(7):E928-35. PMC: 3469619. DOI: 10.1152/ajpendo.00279.2012. View

11.

Knight M, Redman C, Linton E, Sargent I . Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br J Obstet Gynaecol. 1998; 105(6):632-40. DOI: 10.1111/j.1471-0528.1998.tb10178.x. View

12.

Markert M, Andrews P, Babior B . Measurement of O2- production by human neutrophils. The preparation and assay of NADPH oxidase-containing particles from human neutrophils. Methods Enzymol. 1984; 105:358-65. DOI: 10.1016/s0076-6879(84)05048-5. View

13.

Coleman M, Sahai E, Yeo M, Bosch M, Dewar A, Olson M . Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat Cell Biol. 2001; 3(4):339-45. DOI: 10.1038/35070009. View

14.

Baker A, Haeri S, Camargo Jr C, Espinola J, Stuebe A . A nested case-control study of midgestation vitamin D deficiency and risk of severe preeclampsia. J Clin Endocrinol Metab. 2010; 95(11):5105-9. PMC: 2968727. DOI: 10.1210/jc.2010-0996. View

15.

Gargalovic P, Dory L . Cellular apoptosis is associated with increased caveolin-1 expression in macrophages. J Lipid Res. 2003; 44(9):1622-32. DOI: 10.1194/jlr.M300140-JLR200. View

16.

Sabatier F, Roux V, Anfosso F, Camoin L, Sampol J, Dignat-George F . Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood. 2002; 99(11):3962-70. DOI: 10.1182/blood.v99.11.3962. View

17.

Shanker J, Maitra A, Arvind P, Nair J, Dash D, Manchiganti R . Role of vitamin D levels and vitamin D receptor polymorphisms in relation to coronary artery disease: the Indian atherosclerosis research study. Coron Artery Dis. 2011; 22(5):324-32. DOI: 10.1097/MCA.0b013e3283472a57. View

18.

Eis A, Brockman D, Pollock J, Myatt L . Immunohistochemical localization of endothelial nitric oxide synthase in human villous and extravillous trophoblast populations and expression during syncytiotrophoblast formation in vitro. Placenta. 1995; 16(2):113-26. DOI: 10.1016/0143-4004(95)90000-4. View

19.

Guller S, Tang Z, Ma Y, Di Santo S, Sager R, Schneider H . Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia. Placenta. 2010; 32(1):63-9. PMC: 3762591. DOI: 10.1016/j.placenta.2010.10.011. View

20.

Sebbagh M, Renvoize C, Hamelin J, Riche N, Bertoglio J, Breard J . Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001; 3(4):346-52. DOI: 10.1038/35070019. View