Proteasome Levels and Activity in Pregnancies Complicated by Severe Preeclampsia and Hemolysis, Elevated Liver Enzymes, and Thrombocytopenia (HELLP) Syndrome

Autor: Megan Locke, Michelle Axe, Irina A. Buhimschi, Catalin S. Buhimschi, Guomao Zhao, Kathryn Berryman
Rok vydání: 2019
Předmět:
Zdroj: Hypertension. 73:1308-1318
ISSN: 1524-4563
0194-911X
DOI: 10.1161/hypertensionaha.118.12437
Popis: Excessive accumulation of misfolded proteins was recently demonstrated in preeclampsia. We examined levels and activity of circulatory proteasome and immunoproteasome (inflammatory subtype) in preeclampsia and hemolysis, elevated liver enzymes, and thrombocytopenia (HELLP) syndrome. We analyzed samples from women with hypertensive pregnancy disorders (n=115), including preeclampsia with severe features (sPE) and HELLP syndrome, and normotensive controls (n=45). Plasma proteasome and immunoproteasome immunoreactivity were determined by quantifying the α-subunit of the 20S core and β5i (proteasome subunit beta 8 [PSMB8]), respectively. Plasma proteasome activity was analyzed with fluorogenic substrates. MG132, lactacystin, and ONX0914 were used to inhibit the circulating proteasome and immunoproteasome, respectively. Plasma cytokine profiles were evaluated by multiplex immunoassay. Placental expression of β5 (constitutive proteasome) and β5i (immunoproteasome) was interrogated by immunohistochemistry. Women with sPE had increased plasma 20S levels ( P P
Databáze: OpenAIRE