Dysregulation of Promyelocytic Leukemia (PML) Protein Expression in Preeclamptic Placentae

Abstract

Promyelocytic leukemia (PML) protein is a nucleoprotein that can regulate a variety of cellular stress responses. The aim of this study was to determine qualitative and quantitative changes in PML expression in preeclamptic placentae. Immunoblot, qRT-PCR and immunohistochemistry techniques were used to determine PML gene expression and localization in normal (n=6) and preeclamptic (n=6) placentae and primary cells. PML protein was immunolocalized within nuclei of villus mesenchyme, but largely absent in trophoblast nuclei, with a trend for increased PML reactivity in preeclamptic placenta. Immunoblot analyses of nuclear extracts confirmed relative increases (~3 fold) of PML expression in preeclamptic placentae (p<0.05). Conversely, less PML mRNA (~2 fold) was detected in preeclamptic versus normal placental samples. In vitro, PML expression could be increased by hypoxia in cultured endothelial cells but not trophoblast. Increased PML protein expression in preeclamptic villi suggests it could contribute to decreased vascularity and placental growth and/or function.

XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells

“…The mechanism of nuclear apoptosis mediated by AIF is not clear but it results in the activation of nuclear proteins involved in chromatin condensation and DNA degradation [Leavenworth et al 2010]. Local bcl-2 protein has been shown to inhibit the release of AIF from the mitochondrial membranes [Daugas et al 2000;Leavenworth et al 2010]. We observed that PLGF significantly decreases AIF protein expression in serum deprived human primary trophoblasts.…”

“…Apoptosis inducible factor is known to induce apoptosis in vivo as well as in isolated nuclei [Daugas et al 2000;Hisatomi et al 2001]. The mechanism of nuclear apoptosis mediated by AIF is not clear but it results in the activation of nuclear proteins involved in chromatin condensation and DNA degradation [Leavenworth et al 2010]. Local bcl-2 protein has been shown to inhibit the release of AIF from the mitochondrial membranes [Daugas et al 2000;Leavenworth et al 2010].…”

“…The institutional human subjects review committee approved the protocol for collection of the placentae (protocol number 12-575). Classification of PE was according to the American College of Obstetricians and Gynecologist (ACOG) definition of a blood pressure of 140/90 mm Hg or higher, proteinuria 4300 mg/24 h as previously described [Leavenworth et al 2010]. Demographic information of placental tissues is shown in Table 1.…”