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GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia

  • Authors:
    • Junjie Lu
    • Qian Zhang
    • Dongmei Tan
    • Wenping Luo
    • Hai Zhao
    • Jing Ma
    • Hao Liang
    • Yi Tan
  • View Affiliations / Copyright

    Affiliations: Laboratory Animal Center, Chongqing Medical University, Yuzhong, Chongqing 400016, P.R. China
    Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 105-112
    |
    Published online on: May 25, 2016
       https://doi.org/10.3892/ijmm.2016.2608
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Abstract

Gamma-aminobutyric acid (GABA) functions primarily as an inhibitory neurotransmitter through its receptors in the mature central nervous system. The GABA type A receptor π subunit (GABRP) has been identified in the tissues of the reproductive system, particularly in the uterus. In addition, we have previously detected GABRP expression in both human and mouse placentas. To examine the role of GABRP in trophoblastic cell invasion, we constructed a pIRES2-GABRP-EGFP plasmid which was used for the transfection of a human placental cell line derived from first trimester extravillous trophoblasts (HTR-8/SVneo). The number of invaded cells was decreased by GABRP overexpression. Notably, the decrease in the invasive cell number may be due to the increased apoptosis of the HTR-8/SVneo cells following GABRP transfection, which was further confirmed by flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Based on the increased apoptosis of trophoblastic cells in pregnancies complicated by preeclampsia (PE) and the fact that GABRP promotes the apoptosis of trophoblastic cells, we hypothesized that GABRP expression is increased in the placental tissues from patients with PE compared with that in the normal groups and this hypothesis was confirmed by RT-qPCR and immunohistochemical analysis. Taken together, these findings imply that GABRP plays an important role in placentation and this pathway may be a promising molecular target for the development of novel therapeutic strategies for PE.
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1 

Hedblom E and Kirkness EF: A novel class of GABAA receptor subunit in tissues of the reproductive system. J Biol Chem. 272:15346–15350. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Zafrakas M, Chorovicer M, Klaman I, Kristiansen G, Wild PJ, Heindrichs U, Knüchel R and Dahl E: Systematic characterisation of GABRP expression in sporadic breast cancer and normal breast tissue. Int J Cancer. 118:1453–1459. 2006. View Article : Google Scholar

3 

Gladkevich A, Korf J, Hakobyan VP and Melkonyan KV: The peripheral GABAergic system as a target in endocrine disorders. 124:1–8. 2006.

4 

Fujii E and Mellon SH: Regulation of uterine gamma-aminobutyric acid(A) receptor subunit expression throughout pregnancy. Endocrinology. 142:1770–1777. 2001.PubMed/NCBI

5 

Sadeghi H and Taylor HS: HOXA10 regulates endometrial GABAA (pi) receptor expression and membrane translocation. Am J Physiol Endocrinol Metab. 298:E889–E893. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Longtine MS, Chen B, Odibo AO, Zhong Y and Nelson DM: Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR. Placenta. 33:352–359. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Luo W, Liu Z, Tan D, Zhang Q, Peng H, Wang Y and Tan Y: Gamma-amino butyric acid and the A-type receptor suppress decidualization of mouse uterine stromal cells by down-regulating cyclin D3. Mol Reprod Dev. 80:59–69. 2013. View Article : Google Scholar

8 

Allaire AD, Ballenger KA, Wells SR, McMahon MJ and Lessey BA: Placental apoptosis in preeclampsia. Obstet Gynecol. 96:271–276. 2000.PubMed/NCBI

9 

Zhang Q, Chen Q, Lu X, Zhou Z, Zhang H, Lin HY, Duan E, Zhu C, Tan Y and Wang H: CUL1 promotes trophoblast cell invasion at the maternal-fetal interface. Cell Death Dis. 4:e5022013. View Article : Google Scholar : PubMed/NCBI

10 

Sharp AN, Heazell AE, Crocker IP and Mor G: Placental apoptosis in health and disease. Am J Reprod Immunol. 64:159–169. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Straszewski-Chavez SL, Abrahams VM and Mor G: The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev. 26:877–897. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Crocker IP, Cooper S, Ong SC and 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. 162:637–643. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Marzioni D, Mühlhauser J, Crescimanno C, Banita M, Pierleoni C and Castellucci M: BCL-2 expression in the human placenta and its correlation with fibrin deposits. Hum Reprod. 13:1717–1722. 1998. View Article : Google Scholar : PubMed/NCBI

14 

Krajewski S, Krajewska M and Reed JC: Immunohistochemical analysis of in vivo patterns of Bak expression, a proapoptotic member of the Bcl-2 protein family. Cancer Res. 56:2849–2855. 1996.PubMed/NCBI

15 

Cory S, Huang DC and Adams JM: The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 22:8590–8607. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Huppertz B and Kingdom JC: Apoptosis in the trophoblast - role of apoptosis in placental morphogenesis. J Soc Gynecol Investig. 11:353–362. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Huppertz B, Kadyrov M and Kingdom JC: Apoptosis and its role in the trophoblast. Am J Obstet Gynecol. 195:29–39. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Ratts VS, Tao XJ, Webster CB, Swanson PE, Smith SD, Brownbill P, Krajewski S, Reed JC, Tilly JL and Nelson DM: Expression of BCL-2, BAX and BAK in the trophoblast layer of the term human placenta: a unique model of apoptosis within a syncytium. Placenta. 21:361–366. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Murakoshi H, Matsuo H, Laoag-Fernandez JB, Samoto T and Maruo T: Expression of Fas/Fas-ligand, Bcl-2 protein and apoptosis in extravillous trophoblast along invasion to the decidua in human term placenta. Endocr J. 50:199–207. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Ho S, Winkler-Lowen B, Morrish DW, Dakour J, Li H and Guilbert LJ: The role of Bcl-2 expression in EGF inhibition of TNF-alpha/IFN-gamma-induced villous trophoblast apoptosis. Placenta. 20:423–430. 1999. View Article : Google Scholar : PubMed/NCBI

21 

Candelier JJ, Frappart L, Yadaden T, Poaty H, Picard JY, Prévot S and Coullin P: Altered p16 and Bcl-2 expression reflects pathologic development in hydatidiform moles and choriocarcinoma. Pathol Oncol Res. 19:217–227. 2013. View Article : Google Scholar

22 

Lea RG, al-Sharekh N, Tulppala M and Critchley HO: The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies. Hum Reprod. 12:153–158. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Sakuragi N, Matsuo H, Coukos G, Furth EE, Bronner MP, VanArsdale CM, Krajewsky S, Reed JC and Strauss JF III: Differentiation-dependent expression of the BCL-2 proto-oncogene in the human trophoblast lineage. J Soc Gynecol Investig. 1:164–172. 1994.PubMed/NCBI

24 

Huppertz B, Tews DS and Kaufmann P: Apoptosis and syncytial fusion in human placental trophoblast and skeletal muscle. Int Rev Cytol. 205:215–253. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Black S, Kadyrov M, Kaufmann P, Ugele B, Emans N and Huppertz B: Syncytial fusion of human trophoblast depends on caspase 8. Cell Death Differ. 11:90–98. 2004. View Article : Google Scholar

26 

Gauster M, Siwetz M, Orendi K, Moser G, Desoye G and Huppertz B: Caspases rather than calpains mediate remodelling of the fodrin skeleton during human placental trophoblast fusion. Cell Death Differ. 17:336–345. 2010. View Article : Google Scholar

27 

Sizemore GM, Sizemore ST, Seachrist DD and Keri RA: GABA(A) receptor pi (GABRP) stimulates basal-like breast cancer cell migration through activation of extracellular-regulated kinase 1/2 (ERK1/2). J Biol Chem. 289:24102–24113. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Johnson SK and Haun RS: The gamma-aminobutyric acid A receptor pi subunit is overexpressed in pancreatic adenocarcinomas. JOP. 6:136–142. 2005.PubMed/NCBI

29 

Takehara A, Hosokawa M, Eguchi H, Ohigashi H, Ishikawa O, Nakamura Y and Nakagawa H: Gamma-aminobutyric acid (GABA) stimulates pancreatic cancer growth through overexpressing GABAA receptor pi subunit. Cancer Res. 67:9704–9712. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Young SZ and Bordey A: GABA's control of stem and cancer cell proliferation in adult neural and peripheral niches. Physiology (Bethesda). 24:171–185. 2009. View Article : Google Scholar

31 

Watanabe M, Maemura K, Oki K, Shiraishi N, Shibayama Y and Katsu K: Gamma-aminobutyric acid (GABA) and cell proliferation: focus on cancer cells. Histol Histopathol. 21:1135–1141. 2006.PubMed/NCBI

32 

Ortega A: A new role for GABA: inhibition of tumor cell migration. Trends Pharmacol Sci. 24:151–154. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Perry JK, Lins RJ, Lobie PE and Mitchell MD: Regulation of invasive growth: similar epigenetic mechanisms underpin tumour progression and implantation in human pregnancy. Clin Sci (Lond). 118:451–457. 2009. View Article : Google Scholar

34 

Murray MJ and Lessey BA: Embryo implantation and tumor metastasis: common pathways of invasion and angiogenesis. Semin Reprod Endocrinol. 17:275–290. 1999. View Article : Google Scholar

35 

Ferretti C, Bruni L, Dangles-Marie V, Pecking AP and Bellet D: Molecular circuits shared by placental and cancer cells, and their implications in the proliferative, invasive and migratory capacities of trophoblasts. Hum Reprod Update. 13:121–141. 2007. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Lu J, Zhang Q, Tan D, Luo W, Zhao H, Ma J, Liang H and Tan Y: GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia. Int J Mol Med 38: 105-112, 2016.
APA
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J. ... Tan, Y. (2016). GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia. International Journal of Molecular Medicine, 38, 105-112. https://doi.org/10.3892/ijmm.2016.2608
MLA
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J., Liang, H., Tan, Y."GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia". International Journal of Molecular Medicine 38.1 (2016): 105-112.
Chicago
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J., Liang, H., Tan, Y."GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia". International Journal of Molecular Medicine 38, no. 1 (2016): 105-112. https://doi.org/10.3892/ijmm.2016.2608
Copy and paste a formatted citation
x
Spandidos Publications style
Lu J, Zhang Q, Tan D, Luo W, Zhao H, Ma J, Liang H and Tan Y: GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia. Int J Mol Med 38: 105-112, 2016.
APA
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J. ... Tan, Y. (2016). GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia. International Journal of Molecular Medicine, 38, 105-112. https://doi.org/10.3892/ijmm.2016.2608
MLA
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J., Liang, H., Tan, Y."GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia". International Journal of Molecular Medicine 38.1 (2016): 105-112.
Chicago
Lu, J., Zhang, Q., Tan, D., Luo, W., Zhao, H., Ma, J., Liang, H., Tan, Y."GABA A receptor π subunit promotes apoptosis of HTR-8/SVneo trophoblastic cells: Implications in preeclampsia". International Journal of Molecular Medicine 38, no. 1 (2016): 105-112. https://doi.org/10.3892/ijmm.2016.2608
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