Investigation of Bax and Phospho-Tau Protein Expression in Preeclampsia Placenta
Year 2023,
Volume: 20 Issue: 3, 477 - 484, 31.12.2023
Seval Kaya
,
Fırat Aşır
,
Hayat Ayaz
,
Elif Ağaçayak
,
Engin Deveci
Abstract
Background: Preeclampsia is a pregnancy complication with a high morbidity and mortality rate.BAX is a proapoptotic protein and in recent years, 14-3-3 tau proteins are considered as key regulators of many processes, such as apoptosis. In this study, we investigated the expression of phospho-tau and Bax in preeclampsia apoptosis immunohistochemically.
Materials and Methods: 25 healthy and 25 preeclamptic pregnant placentas were included in the study. Placental samples were fixed with 10% neutral buffered formalin. Routine paraffin wax tissue protocol was used.
Results: According to histological micrograf, the trophoblastic cells in the villi were normal in the control group. Mild dilatation in blood vessels was seen. Hyalinized and necrotic areas in chorionic villi and an increase in fibrinoid tissue in root villi were detected in preeclampsia sections. Phospho-tau and Bax primary antibodys were used for immunohistochemical evaluation. The sections from of the preeclampsia group were highly positive for syncytiotrophoblasts and villous connective tissue. It was also statistically different from the control group (p<0.05).
Conclusions: When we evaluate the results shows that Phospho-tau and Bax may be determinant proteins in the apoptosis pathway of preeclampsia.
References
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- 8. Rana S, Lemoine E, Granger J, Karumanchi SA. Preeclamp-sia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019;124(7):1094–112.
- 9. Lyall F. The Human Placental Bed Revisited. Placenta. 2002;23(8–9):555–62.
- 10. Vanwijk MJ, Kublickiene K, Boer K, VanBavel E. Vascular function in preeclampsia. Cardiovasc Res. 2000;47(1):38–48.
- 11. Mohammadpour-Gharehbagh A, jahantigh D, Eskandari M, Sadegh MH, Nematollahi MH, Rezaei M, et al. Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia. Apoptosis. 2019;24(3–4):301–11.
- 12. Sircar M, Thadhani R, Karumanchi SA. Pathogenesis of preeclampsia. Curr Opin Nephrol Hypertens. 2015;24(2):131–8.
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- 14. Situmorang PC, Ilyas S. Study of Preeclampsia in Placenta, Kidney, and Hepatic Diseases. Asian Journal of Pharmaceu-tical and Clinical Research. 2018;11(11):21–8.
- 15. Chen Y, Xue F, Han C, Yang H, Han L, Li K, et al. Ferulic acid ameliorated placental inflammation and apoptosis in rat with preeclampsia. Clin Exp Hypertens. 2019;41(6):524–30.
- 16. Nomura M, Shimizu S, Sugiyama T, Narita M, Ito T, Matsu-da H, et al. 14-3-3 Interacts Directly with and Negatively Regulates Pro-apoptotic Bax. Journal of Biological Che-mistry. 2003;278(3):2058–65.
- 17. Rosenquist M. 14-3-3 proteins in apoptosis. Braz J Med Biol Res. 2003;36(4):403–8.
- 18. Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsuji-moto Y, et al. JNK promotes Bax translocation to mitoc-hondria through phosphorylation of 14-3-3 proteins. EMBO Journal. 2004;23(8):1889–99.
- 19. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. The Lancet. 2001;357(9249):53–6.
- 20. Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental Apop-tosis in Health and Disease. American Journal of Reproduc-tive Immunology. 2010;64(3):159–69.
- 21. Bell MJ. A historical overview of preeclampsia-eclampsia. J Obstet Gynecol Neonatal Nurs. 2010;39(5):510–8.
- 22. Sgarbosa F, Barbisan LF, Brasil MAM, Costa E, Calderon IMP, Gonçalves CR, et al. Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trop-hoblast. Diabetes Res Clin Pract. 2006;73(2):143–9.
- 23. Hecht JL, Zsengeller ZK, Spiel M, Karumanchi SA, Rosen S. Revisiting decidual vasculopathy. Placenta. 2016;42:37–43.
- 24. Costa E, Cunha Castro DA, Popek E, Cunha D, Ec C, Abnor-malities PE, et al. Abnormalities of placenta implantation. APMIS. 2018;126(7):613–20.
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- 27. Cobellis L, De Falco M, Torella M, Trabucco E, Caprio F, Federico E, et al. Modulation of Bax Expression in Physio-logical and Pathological Human Placentas Throughout Pregnancy. In Vivo (Brooklyn) 2007;21(5):777–83.
- 28. Gokalp-Ozkorkmaz E, Asir F, Basaran SO, Agacayak E, Sahin F, Kaya S, et al. Examination of Bcl-2 and Bax Protein Levels for Determining the Apoptotic Changes in Placentas with Gestational Diabetes and Preeclampsia. Proceedings 2018;2(25):1548.
- 29. Twohig D, Nielsen HM. α-synuclein in the pathophysiology of Alzheimer’s disease. Mol Neurodegener. 2019;14(1).
- 30. Liu H, Tang Y, Liu X, Zhou Q, Xiao X, Lan F, et al. 14-3-3 tau (YWHAQ) gene promoter hypermethylation in human pla-centa of preeclampsia. Placenta. 2014;35(12):981–8.
- 31. Park JK, Kang MY, Kim YH, Jo HC, Shin JK, Choi WJ, et al. PKC delta in preeclamptic placentas promotes Bax dissocia-tion from 14-3-3 zeta through 14-3-3 zeta phosphorylation. Placenta. 2008;29(7):584–92.
- 32. Knight M, Redman CWG, Linton EA, Sargent IL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. BJOG. 1998;105(6):632–40.
- 33. Machaalani R, Makris A, Thornton C, Hennessy A. Vascular endothelial growth factor receptor 1 (Flt1) and apoptosis in the preeclamptic placenta and effects of in vivo anti-hypertensive exposure. Hypertens Pregnancy. 2008;27(4):361–73.
- 34. Raguema N, Moustadraf S, Bertagnolli M. Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Front Physiol. 2020;11;11:98.
Preeklampsi Plasentada Bax ve Fosfo-Tau Protein Ekspresyonunun Araştırılması
Year 2023,
Volume: 20 Issue: 3, 477 - 484, 31.12.2023
Seval Kaya
,
Fırat Aşır
,
Hayat Ayaz
,
Elif Ağaçayak
,
Engin Deveci
Abstract
Amaç: Preeklampsi, morbidite ve mortalite oranı yüksek bir gebelik komplikasyonudur. Bax proapoptotik bir proteindir ve son yıllarda 14-3-3 tau proteinleri, apoptoz gibi birçok sürecin anahtar düzenleyicileri olarak kabul edilmektedir. Bu çalışmada preeklampsi apoptozunda fosfo-tau ve Bax ekspresyonunu immünohistokimyasal olarak araştırdık.
Materyal ve Metod: 25 sağlıklı ve 25 preeklamptik gebe plasenta çalışmaya dahil edildi. Plasental örnekler %10 nötr tamponlu formalinle sabitlendi. Rutin parafin mum doku protokolü kullanıldı.
Bulgular: Histolojik sonuçlara göre kontrol grubunda villuslardaki trofoblastik hücreler normaldi. Ve kan damarlarında hafif genişleme görüldü. Preeklampsi kesitlerinde koryon villuslarında hyalinize ve nekrotik alanlar ve kök villuslarında fibrinoid doku artışı saptandı. İmmünohistokimyasal değerlendirme için fosfo-tau ve Bax primer antikorları kullanıldı. Preeklampsi grubundan alınan kesitler sinsityotrofoblastlar ve villöz bağ dokusu açısından oldukça pozitifti. Kontrol grubundan istatistiksel olarak da farklıydı (p<0.05).
Sonuç: Bulguları incelediğimizde, Phospho-tau ve Bax'ın preeklampsinin apoptoz yolağında belirleyici proteinler olabilir
References
- 1. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130–7.
- 2. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Manage-ment Recommendations for International Practice. Hyper-tension. 2018;72(1):24–43.
- 3. Ghulmiyyah L, Sibai B. Maternal mortality from preeclamp-sia/eclampsia. Semin Perinatol. 2012;36(1):56–9.
- 4. Wanderer JP, Leffert LR, Mhyre JM, Kuklina E V., Callaghan WM, Bateman BT. Epidemiology of obstetric-related ICU admissions in Maryland: 1999-2008*. Crit Care Med. 2013;41(8):1844–52.
- 5. Kuklina E V., Ayala C, Callaghan WM. Hypertensive disor-ders and severe obstetric morbidity in the United States. Obstetrics and gynecology. 2009;113(6):1299–306.
- 6. Gathiram P, Moodley J. pre-eclampsia: its pathogenesis and pathophysiolgy. Cardıovascular J. of Afrıca. 2016;27(2):71–8.
- 7. Phipps E, Prasanna D, Brima W, Jim B. Preeclampsia: Upda-tes in Pathogenesis, Definitions, and Guidelines. Clin J Am Soc Nephrol. 2016;11(6):1102–13.
- 8. Rana S, Lemoine E, Granger J, Karumanchi SA. Preeclamp-sia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019;124(7):1094–112.
- 9. Lyall F. The Human Placental Bed Revisited. Placenta. 2002;23(8–9):555–62.
- 10. Vanwijk MJ, Kublickiene K, Boer K, VanBavel E. Vascular function in preeclampsia. Cardiovasc Res. 2000;47(1):38–48.
- 11. Mohammadpour-Gharehbagh A, jahantigh D, Eskandari M, Sadegh MH, Nematollahi MH, Rezaei M, et al. Genetic and epigenetic analysis of the BAX and BCL2 in the placenta of pregnant women complicated by preeclampsia. Apoptosis. 2019;24(3–4):301–11.
- 12. Sircar M, Thadhani R, Karumanchi SA. Pathogenesis of preeclampsia. Curr Opin Nephrol Hypertens. 2015;24(2):131–8.
- 13. Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Maruo T. Increased apoptosis in the syncytiot-rophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol. 2002;186(1):158–66.
- 14. Situmorang PC, Ilyas S. Study of Preeclampsia in Placenta, Kidney, and Hepatic Diseases. Asian Journal of Pharmaceu-tical and Clinical Research. 2018;11(11):21–8.
- 15. Chen Y, Xue F, Han C, Yang H, Han L, Li K, et al. Ferulic acid ameliorated placental inflammation and apoptosis in rat with preeclampsia. Clin Exp Hypertens. 2019;41(6):524–30.
- 16. Nomura M, Shimizu S, Sugiyama T, Narita M, Ito T, Matsu-da H, et al. 14-3-3 Interacts Directly with and Negatively Regulates Pro-apoptotic Bax. Journal of Biological Che-mistry. 2003;278(3):2058–65.
- 17. Rosenquist M. 14-3-3 proteins in apoptosis. Braz J Med Biol Res. 2003;36(4):403–8.
- 18. Tsuruta F, Sunayama J, Mori Y, Hattori S, Shimizu S, Tsuji-moto Y, et al. JNK promotes Bax translocation to mitoc-hondria through phosphorylation of 14-3-3 proteins. EMBO Journal. 2004;23(8):1889–99.
- 19. Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. The Lancet. 2001;357(9249):53–6.
- 20. Sharp AN, Heazell AEP, Crocker IP, Mor G. Placental Apop-tosis in Health and Disease. American Journal of Reproduc-tive Immunology. 2010;64(3):159–69.
- 21. Bell MJ. A historical overview of preeclampsia-eclampsia. J Obstet Gynecol Neonatal Nurs. 2010;39(5):510–8.
- 22. Sgarbosa F, Barbisan LF, Brasil MAM, Costa E, Calderon IMP, Gonçalves CR, et al. Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trop-hoblast. Diabetes Res Clin Pract. 2006;73(2):143–9.
- 23. Hecht JL, Zsengeller ZK, Spiel M, Karumanchi SA, Rosen S. Revisiting decidual vasculopathy. Placenta. 2016;42:37–43.
- 24. Costa E, Cunha Castro DA, Popek E, Cunha D, Ec C, Abnor-malities PE, et al. Abnormalities of placenta implantation. APMIS. 2018;126(7):613–20.
- 25. Sharp AN, Heazell AEP, Baczyk D, Dunk CE, Lacey HA, Jones CJP, et al. Preeclampsia Is Associated with Alterations in the p53-Pathway in Villous Trophoblast. PLoS One. 2014;9(1):87621.
- 26. Daher S, Guimarães AJ, Mattar R, Ishigai MMS, Barreiro EG, Bevilacqua EB. Bcl-2 and Bax expressions in pre-term, term and post-term placentas. Am J Reprod Immunol. 2008;60(2):172–8.
- 27. Cobellis L, De Falco M, Torella M, Trabucco E, Caprio F, Federico E, et al. Modulation of Bax Expression in Physio-logical and Pathological Human Placentas Throughout Pregnancy. In Vivo (Brooklyn) 2007;21(5):777–83.
- 28. Gokalp-Ozkorkmaz E, Asir F, Basaran SO, Agacayak E, Sahin F, Kaya S, et al. Examination of Bcl-2 and Bax Protein Levels for Determining the Apoptotic Changes in Placentas with Gestational Diabetes and Preeclampsia. Proceedings 2018;2(25):1548.
- 29. Twohig D, Nielsen HM. α-synuclein in the pathophysiology of Alzheimer’s disease. Mol Neurodegener. 2019;14(1).
- 30. Liu H, Tang Y, Liu X, Zhou Q, Xiao X, Lan F, et al. 14-3-3 tau (YWHAQ) gene promoter hypermethylation in human pla-centa of preeclampsia. Placenta. 2014;35(12):981–8.
- 31. Park JK, Kang MY, Kim YH, Jo HC, Shin JK, Choi WJ, et al. PKC delta in preeclamptic placentas promotes Bax dissocia-tion from 14-3-3 zeta through 14-3-3 zeta phosphorylation. Placenta. 2008;29(7):584–92.
- 32. Knight M, Redman CWG, Linton EA, Sargent IL. Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. BJOG. 1998;105(6):632–40.
- 33. Machaalani R, Makris A, Thornton C, Hennessy A. Vascular endothelial growth factor receptor 1 (Flt1) and apoptosis in the preeclamptic placenta and effects of in vivo anti-hypertensive exposure. Hypertens Pregnancy. 2008;27(4):361–73.
- 34. Raguema N, Moustadraf S, Bertagnolli M. Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Front Physiol. 2020;11;11:98.