Investigation of Prohibitin Levels in Preeclampsia Cases: A Case Control Study from a Tertiary Hospital

Year 2025, Volume: 4 Issue: 1, 15 - 21, 27.03.2025

Hasan Burak Keser , Funda Gülcü Bulmuş , Salih Kavak , Ebru Çelik Kavak

Abstract

Introductıon: To evaluate the relationship between the effects of prohibitin at the cellular level and the pathophysiology of preeclampsia.
Methods: This study included a total of 120 patients who presented to our clinic at 20–41 weeks of gestation. The participants were divided into three groups: 40 pregnant women with preeclampsia with severe features, 40 pregnant women with preeclampsia, and 40 healthy pregnant women. To measure serum prohibitin levels, 10 cc of venous blood was collected from each participant, and comparisons were made between the groups.
Results: Serum prohibitin levels were significantly higher in pregnant women with preeclampsia with severe features and preeclampsia compared to the control group (p<0.001 for both).
Conclusion: Prohibitin levels were found to be significantly increased in pregnant women with preeclampsia with severe features and those with preeclampsia compared to healthy pregnant women, suggesting that prohibitin may serve as a marker of preeclampsia.

Keywords

Prohibitin, Preeclampsia, Pregnant, Oxidative stress, Apoptosis

References

• 1. Higgins JR, de Swiet M. Blood-pressure measurement and classification in pregnancy. Lancet. 2001;357(9250):131-5. doi: 10.1016/s0140-6736(00)03552-2. PubMed PMID: 11197413.
• 2. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019;124(7):1094-112. doi: 10.1161/circresaha.118.313276. PubMed PMID: 30920918.
• 3. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785-99. doi: 10.1016/s0140-6736(05)17987-2. PubMed PMID: 15733721.
• 4. Wu P, Green M, Myers JE. Hypertensive disorders of pregnancy. Bmj. 2023;381:e071653. Epub 20230630. doi: 10.1136/bmj-2022-071653. PubMed PMID: 37391211.
• 5. McClung JK, Danner DB, Stewart DA, Smith JR, Schneider EL, Lumpkin CK, et al. Isolation of a cDNA that hybrid selects antiproliferative mRNA from rat liver. Biochem Biophys Res Commun. 1989;164(3):1316-22. doi: 10.1016/0006-291x(89)91813-5. PubMed PMID: 2480116.
• 6. Osman C, Haag M, Potting C, Rodenfels J, Dip PV, Wieland FT, et al. The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria. J Cell Biol. 2009;184(4):583-96. Epub 20090216. doi: 10.1083/jcb.200810189. PubMed PMID: 19221197; PubMed Central PMCID: PMC2654118.
• 7. Mishra S, Murphy LC, Murphy LJ. The Prohibitins: emerging roles in diverse functions. J Cell Mol Med. 2006;10(2):353-63. doi: 10.1111/j.1582-4934.2006.tb00404.x. PubMed PMID: 16796804; PubMed Central PMCID: PMC3933126.
• 8. Ande SR, Nguyen KH, Nyomba BLG, Mishra S. Prohibitin in Adipose and Immune Functions. Trends Endocrinol Metab. 2016;27(8):531-41. Epub 20160613. doi: 10.1016/j.tem.2016.05.003. PubMed PMID: 27312736.
• 9. Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, Hall PA, et al. Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Exp Cell Res. 2001;265(2):262-73. doi: 10.1006/excr.2001.5166. PubMed PMID: 11302691.
• 10. Nijtmans LG, de Jong L, Artal Sanz M, Coates PJ, Berden JA, Back JW, et al. Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins. Embo j. 2000;19(11):2444-51. doi: 10.1093/emboj/19.11.2444. PubMed PMID: 10835343; PubMed Central PMCID: PMC212747.
• 11. Theiss AL, Idell RD, Srinivasan S, Klapproth JM, Jones DP, Merlin D, et al. Prohibitin protects against oxidative stress in intestinal epithelial cells. Faseb j. 2007;21(1):197-206. Epub 20061129. doi: 10.1096/fj.06-6801com. PubMed PMID: 17135366.
• 12. Scherz-Shouval R, Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci. 2011;36(1):30-8. Epub 20100820. doi: 10.1016/j.tibs.2010.07.007. PubMed PMID: 20728362.
• 13. Abbas Y, Turco MY, Burton GJ, Moffett A. Investigation of human trophoblast invasion in vitro. Hum Reprod Update. 2020;26(4):501-13. doi: 10.1093/humupd/dmaa017. PubMed PMID: 32441309; PubMed Central PMCID: PMC7473396.
• 14. Melchiorre K, Giorgione V, Thilaganathan B. The placenta and preeclampsia: villain or victim?Am J Obstet Gynecol. 2022;226(2s):S954-s62. Epub 20210324. doi: 10.1016/j.ajog.2020.10.024. PubMed PMID: 33771361.
• 15. Tomimatsu T, Mimura K, Matsuzaki S, Endo M, Kumasawa K, Kimura T. Preeclampsia: Maternal Systemic Vascular Disorder Caused by Generalized Endothelial Dysfunction Due to Placental Antiangiogenic Factors. Int J Mol Sci. 2019;20(17). Epub 20190830. doi: 10.3390/ijms20174246. PubMed PMID: 31480243; PubMed Central PMCID: PMC6747625.
• 16. Leijnse JEW, de Heus R, de Jager W, Rodenburg W, Peeters LLH, Franx A, et al. First trimester placental vascularization and angiogenetic factors are associated with adverse pregnancy outcome. Pregnancy Hypertens. 2018;13:87-94. Epub 20180411. doi: 10.1016/j.preghy.2018.04.008. PubMed PMID: 30177079.
• 17. Tanacan A, Fadiloglu E, Beksac MS. The importance of proteinuria in preeclampsia and its predictive role in maternal and neonatal outcomes. Hypertens Pregnancy. 2019;38(2):111-8. Epub 20190402. doi: 10.1080/10641955.2019.1590718. PubMed PMID: 30939965.
• 18. Smith SC, Leung TN, To KF, Baker PN. Apoptosis is a rare event in first-trimester placental tissue. Am J Obstet Gynecol. 2000;183(3):697-9. doi: 10.1067/mob.[phone]. PubMed PMID: 10992195.
• 19. Ashton SV, Whitley GS, Dash PR, Wareing M, Crocker IP, Baker PN, et al. Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions. Arterioscler Thromb Vasc Biol. 2005;25(1):102-8. Epub 20041021. doi: 10.1161/01.Atv.0000148547.70187.89. PubMed PMID: 15499040; PubMed Central PMCID: PMC4228192.
• 20. Abrahams VM, Straszewski-Chavez SL, Guller S, Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol Hum Reprod. 2004;10(1):55-63. doi: 10.1093/molehr/gah006. PubMed PMID: 14665707.
• 21. Huppertz B, Frank HG, Kingdom JC, Reister F, Kaufmann P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol. 1998;110(5):495-508. doi: 10.1007/s004180050311. PubMed PMID: 9826129.
• 22. Genbacev O, DiFederico E, McMaster M, Fisher SJ. Invasive cytotrophoblast apoptosis in pre-eclampsia. Hum Reprod. 1999;14 Suppl 2:59-66. doi: 10.1093/humrep/14.suppl_2.59. PubMed PMID: 10690801.
• 23. Crocker IP, Cooper S, Ong SC, Baker PN. Differences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol. 2003;162(2):637-43. doi: 10.1016/s0002-9440(10)63857-6. PubMed PMID: 12547721; PubMed Central PMCID: PMC1851173.
• 24. Mishra S, Nyomba BG. Prohibitin: A hypothetical target for sex-based new therapeutics for metabolic and immune diseases. Exp Biol Med (Maywood). 2019;244(2):157-70. Epub 20190204. doi: 10.1177/1535370219828362. PubMed PMID: 30717609; PubMed Central PMCID: PMC6405819.
• 25. Nuell MJ, Stewart DA, Walker L, Friedman V, Wood CM, Owens GA, et al. Prohibitin, an evolutionarily conserved intracellular protein that blocks DNA synthesis in normal fibroblasts and HeLa cells. Mol Cell Biol. 1991;11(3):1372-81. doi: 10.1128/mcb.11.3.1372-1381.1991. PubMed PMID: 1996099; PubMed Central PMCID: PMC369408.
• 26. Sosa V, Moliné T, Somoza R, Paciucci R, Kondoh H, ME LL. Oxidative stress and cancer: an overview. Ageing Res Rev. 2013;12(1):376-90. Epub 20121031. doi: 10.1016/j.arr.2012.10.004. PubMed PMID: 23123177.
• 27. Chiarello DI, Abad C, Rojas D, Toledo F, Vázquez CM, Mate A, et al. Oxidative stress: Normal pregnancy versus preeclampsia. Biochim Biophys Acta Mol Basis Dis. 2020;1866(2):165354. Epub 20181224. doi: 10.1016/j.bbadis.2018.12.005. PubMed PMID: 30590104.
• 28. Mishra S, Murphy LC, Nyomba BL, Murphy LJ. Prohibitin: a potential target for new therapeutics. Trends Mol Med. 2005;11(4):192-7. doi: 10.1016/j.molmed.2005.02.004. PubMed PMID: 15823758.
• 29. Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA. Placental apoptosis in preeclampsia. Obstet Gynecol. 2000;96(2):271-6. doi: 10.1016/s0029-7844(00)00895-4. PubMed PMID: 10908776.
• 30. Jupe ER, Liu XT, Kiehlbauch JL, McClung JK, Dell’Orco RT. Prohibitin antiproliferative activity and lack of heterozygosity in immortalized cell lines.Exp Cell Res. 1995;218(2):577-80. doi: 10.1006/excr.1995.1194. PubMed PMID: 7796893.
• 31. Rusterholz C, Hahn S, Holzgreve W. Role of placentally produced inflammatory and regulatory cytokines in pregnancy and the etiology of preeclampsia. Semin Immunopathol. 2007;29(2):151-62. doi: 10.1007/s00281-007-0071-6. PubMed PMID: 17621700.
• 32. Wang D, Tabti R, Elderwish S, Abou-Hamdan H, Djehal A, Yu P, et al. Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases. Cell Mol Life Sci. 2020;77(18):3525-46. Epub 20200215. doi: 10.1007/s00018-020-03475-1. PubMed PMID: 32062751; PubMed Central PMCID: PMC11104971.
• 33. Jung E, Romero R, Yeo L, Gomez-Lopez N, Chaemsaithong P, Jaovisidha A, et al. The etiology of preeclampsia. Am J Obstet Gynecol. 2022;226(2s):S844-s66. doi: 10.1016/j.ajog.2021.11.1356. PubMed PMID: 35177222; PubMed Central PMCID: PMC8988238.