Altered expression of p97/Valosin containing protein and impairedautophagy in preeclamptic human placenta     
Yazarlar (6)
Prof. Dr. Asker Zeki ÖZSOY Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Sevil Cayli
Ankara Yildirim Beyazit University, Türkiye
Cansu Sahin
Ankara Yildirim Beyazit University, Türkiye
Seda Ocakli
Ankara Yildirim Beyazit University, Türkiye
Tuba Ozdemir Sanci
Ankara Yildirim Beyazit University, Türkiye
Delibas Bahri Ilhan
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı Placenta
Dergi ISSN 0143-4004 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI
Dergi Grubu Q4
Makale Dili İngilizce
Basım Tarihi 01-2018
Cilt No 67
Sayı 1
Sayfalar 45 / 53
DOI Numarası 10.1016/j.placenta.2018.05.013
Özet
Introduction: Autophagy increases in placenta-related obstetrical diseases such as preeclampsia and intrauterine growth retardation but the regulation of autophagy by ubiquitin proteasome pathway (UPP) proteins, p97/Valosin containing protein (VCP) and ubiquitin (Ub) have not been previuosly studied in preeclampsia. The objective of this study is to investigate the expression of UPP (p97/VCP and Ub), autophagosomal (p62 and LC3) and autolysosomal proteins (Lamp1 and Lamp2) in the normal and preeclamptic human placentas and to explore the regulatory mechanism of these proteins in autophagic pathway. Material and methods: Different portions of normal term placentas (n = 20) and preeclamptic placentas (n = 10) were snap-frozen in liquid nitrogen for Western blotting and coimmunoprecipitation and others were fixed-embedded in paraffin for immunohistochemistry. Colocalization and coimmunoprecipitation experiments were done for the detection of interaction between p97/VCP and autophagic proteins. Results: Compared with normal placentas, expression of p97/VCP was significantly reduced; however accumulation of ubiquitinlated proteins were significantly increased in preeclamptic placentas. The expression of autophagosomal proteins (LC3-II and p62) were significantly increased and no significant alterations of the expression of autolysosomal proteins were observed in preeclamptic placentas. Additionally, p97/VCP was found to colocalized and interact with autophagosomal and autolysosomal markers in normal and preeclamptic placentas. Autophagosome maturation diminished and autophagosomes had decreased localization with lysosomal markers in preeclamptic human placentas. Conclusion: Decreased expression of p97/VCP and increased expression of Ub in preeclampsia might be related to impaired autophagy and pathophysiology of preeclampsia. Therefore, our study highlights an important potential relationship between p97/VCP and autophagic proteins in preeclampsia.
Anahtar Kelimeler
Autophagy | Human placenta | p97/VCP | Preeclampsia | Ubiquitin