Altered expression of p97/Valosin containing protein and impaired autophagy in preeclamptic human placenta
Asker Zeki Ozsoy1, Sevil Cayli2, Cansu Sahin2
1Gaziosmanpasa University, Medical Faculty, Dept. of Obstetrics and Gynecology, Tokat, Turkey.
Insights
In preeclampsia, reduced p97/Valosin containing protein (VCP) and increased ubiquitin (Ub) correlate with impaired autophagy. This study reveals a potential link between p97/VCP and autophagic proteins in preeclampsia pathophysiology.
Area of Science:
- Cell Biology
- Obstetrics and Gynecology
- Biochemistry
Background:
- Autophagy is elevated in placenta-related disorders like preeclampsia.
- The role of ubiquitin proteasome pathway (UPP) proteins, specifically p97/Valosin containing protein (VCP) and ubiquitin (Ub), in preeclampsia-related autophagy remains unstudied.
Purpose of the Study:
- To investigate the expression of UPP proteins (p97/VCP, Ub), autophagosomal proteins (p62, LC3), and autolysosomal proteins (Lamp1, Lamp2) in normal and preeclamptic human placentas.
- To explore the regulatory mechanisms of these proteins within the autophagic pathway in preeclampsia.
Main Methods:
- Western blotting and coimmunoprecipitation were performed on normal (n=20) and preeclamptic (n=10) placental tissues.
- Immunohistochemistry, colocalization, and coimmunoprecipitation experiments were utilized to detect protein interactions.
Main Results:
- Preeclamptic placentas showed significantly reduced p97/VCP expression and increased Ub accumulation compared to normal placentas.
- Autophagosomal proteins (LC3-II, p62) were significantly increased, while autolysosomal proteins showed no significant alteration.
- p97/VCP interacted with autophagosomal and autolysosomal markers, but autophagosome maturation and lysosomal localization were diminished in preeclampsia.
Conclusions:
- Decreased p97/VCP and increased Ub in preeclampsia may contribute to impaired autophagy and the disease's pathophysiology.
- This study highlights a significant potential relationship between p97/VCP and autophagic proteins in the context of preeclampsia.
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.
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