Proteomic Analysis of Hypoxia-Induced Responses in the Syncytialization of Human Placental Cell Line BeWo

Hu, R.; Jin, H.; Zhou, S.; Yang, P.; Li, X.

doi:10.1016/j.placenta.2006.07.005

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Volume 28, Issue 5 , Pages 399-407, May 2007

Proteomic Analysis of Hypoxia-Induced Responses in the Syncytialization of Human Placental Cell Line BeWo

R. Hu
- Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China
- The first two authors equally contributed to this article.
H. Jin
- Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
- Institute of Biomedical Science, Fudan University, Shanghai, China
- The first two authors equally contributed to this article.
S. Zhou
- Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore
P. Yang
- Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
- Institute of Biomedical Science, Fudan University, Shanghai, China
- Corresponding author. Tel./fax: +86 21 6564 2009.
X. Li
- Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Road, Shanghai 200011, China
- Corresponding author. Tel.: +86 21 6377 0161x228; fax: +86 21 6377 0768.

Accepted 10 July 2006. published online 15 November 2006.

Abstract

Syncytiotrophoblast formation is affected by a number of pathological conditions and suppressed syncytiotrophoblast formation due to hypoxia may play a role in the pathogenesis of preeclampsia. However, the molecular basis of hypoxia-inhibited trophoblast syncytialization is poorly understood. To determine the effect of hypoxia on trophoblast syncytialization, a proteomic analysis was performed in the human cytotrophoblast cell line BeWo using two-dimensional electrophoresis and MALDI-TOF-TOF-MS. Hypoxia induced marked inhibition of BeWo cell fusion and differentiation. The proteomic profiling was established under hypoxia in BeWo cell syncytialization. The results showed that twenty proteins were significantly up-or down-regulated under hypoxia, compared with cells under normoxia. In response to hypoxia, three antioxidants, peroxiredoxin 1, peroxiredoxin 2 and 1-Cys peroxiredoxin, were down-regulated, two proteins involved in glycolysis pathway (malate dehydrogenase and enolase) were up-regulated. The expression of two members of the annexin family (annexin A2 and annexin A5) increased. We also found a decreased expression of 14-3-3 tau protein in hypoxia treated cells. Proteins implied in protein degradation and folding were also identified. The expression of two cytoskeleton components (keratin 1 and β-actin) was found to be down-regulated. In addition, galectin-3 was up-regulated. These proteins have been implicated in regulating cellular oxidative stress, glycolysis, signal transduction, protein folding and degradation, cell mobility and cytoskeletal structure formation. Western blot analysis revealed that the levels of peroxiredoxin 1 and 14-3-3 tau decreased, whereas the levels of annexin A5 and annexin A2 increased in BeWo cells under hypoxia. These findings provided new insights into the molecular mechanisms in mediating cellular response to hypoxia in trophoblast syncytialization.

Keywords: Proteomics, Hypoxia, Syncytialization, Placenta, BeWo cell