Reduced syncytin-1 expression in choriocarcinoma BeWo cells activates the calpain1–AIF-mediated apoptosis, implication for preeclampsia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-08

AUTHORS

Qiang Huang, Haibin Chen, Fengchao Wang, Brian C. Brost, Jinping Li, Yu Gao, Zongfang Li, Ya Gao, Shi-Wen Jiang

ABSTRACT

Placentas associated with preeclampsia are characterized by extensive apoptosis in trophoblast lineages. Syncytin-1 (HERVWE1) mediates the fusion of cytotrophoblasts to form syncytiotrophoblasts, which assume the placental barrier, fetal-maternal exchange and endocrine functions. While decreased syncytin-1 expression has been observed in preeclamptic placentas, it is not clear if this alteration is involved in trophoblast apoptosis. In the current study, we found that siRNA-mediated knockdown of syncytin-1 led to apoptosis in choriocarcinoma BeWo, a cell line of trophoblastic origin. Characterization of the apoptotic pathways indicated that this effect does not rely on the activation of caspases. Rather, decreased syncytin-1 levels activated the apoptosis inducing factor (AIF) apoptotic pathway by inducing the expression, cleavage, and nuclear translocation of AIF. Moreover, calpain1, the cysteine protease capable of cleaving AIF, was upregulated by syncytin-1 knockdown. Furthermore, treatment with calpain1 inhibitor MDL28170 effectively reversed AIF cleavage, AIF nuclear translocation, and cell apoptosis triggered by syncytin-1 downregulation, verifying the specific action of calpain1-AIF pathway in trophoblast apoptosis. We confirmed that preeclamptic placentas express lower levels of syncytin-1 than normal placentas, and observed an inverse correlation between syncytin-1 and AIF/calpain1 mRNA levels, a result consistent with the in vitro findings. Immunohistochemistry analyses indicated decreased syncytin-1 and increased AIF and calpain1 protein levels in apoptotic cells of preeclamptic placentas. These findings have for the first time revealed that decreased levels of syncytin-1 can trigger the AIF-mediated apoptosis pathway in BeWo cells. This novel mechanism may contribute to the structural and functional deficiencies of syncytium frequently observed in preeclamptic placentas. More... »

PAGES

3151-3164

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00018-013-1533-8

DOI

http://dx.doi.org/10.1007/s00018-013-1533-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029992109

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24413738


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