Oxidized Transthyretin in Amniotic Fluid as an Early Marker of Preeclampsia

Vascotto, Carlo; Salzano, Anna Maria; D’Ambrosio, Chiara; Fruscalzo, Arrigo; Marchesoni, D.; Loreto, Carla Di; Scaloni, Andrea; Tell, Gianluca; Quadrifoglio, Franco

doi:10.1021/pr060315z

Cited by 69 publications

(52 citation statements)

References 42 publications

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“…Given its apparent molecular weight by 2DE, the upregulated transthyretin in our study may well have been dimeric. Monomeric transthyretin has been reported at higher levels in amniotic fluid of women who subsequently developed preeclampsia, possibly as a result of oxidative stress that acts as a major destabilizing factor of the functional dimeric form (49). Once transthyretin dissociates into monomers, it can undergo tertiary structural changes to form amyloid fibrils (50).…”

Section: Discussionmentioning

confidence: 99%

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Atkinson

Blumenstein

Black³

et al. 2009

Journal of Lipid Research

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Preeclampsia is a common pregnancy complication that is an important cause of preterm birth and fetal growth restriction. Because there is no diagnostic test yet available for preeclampsia, we used a proteomic approach to identify novel serum/plasma biomarkers for this condition. We conducted case control studies comparing nulliparous women who developed preeclampsia at 36-38 weeks of gestation with healthy nulliparous women matched by gestational age at sampling. Serum/plasma was depleted of six abundant proteins and analyzed by two-dimensional gel electrophoresis (n 5 12 per group) and difference gel electrophoresis (n 5 12 per group). Differences in abundance of protein spots were detected by univariate and multivariate statistical analyses. Proteins were identified by mass spectrometry and expression of selected proteins was validated by immunoblotting. Proteins whose concentrations were selectively associated with preeclampsia included apolipoprotein E (apoE), apoC-II, complement factor C3c, fibrinogen, transthyretin, and complement factor H-related protein 2. An increase in a deglycosylated isoform of apoE3 and concomitantly decreased amounts of one apoE3 glycoisoform were identified in preeclamptic plasma and confirmed by immunoblotting. Altered production of these preeclampsia-related apoE3 isoforms might impair reverse cholesterol transport, contributing to arterial damage. These findings point to a novel mechanistic link between preeclampsia and subsequent cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Atkinson

Blumenstein

Black³

et al. 2009

Journal of Lipid Research

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“…Damage caused by oxidative stress, including changes to DNA and proteins, as well as the mechanisms of DNA repair, appears to play a key role in obstetrical pathologies of placental origin, including PE and IUGR (Vascotto et al 2007;Takagi et al 2004;Kimura et al 2013;Rossi et al 2013;Tamura et al 2011). In this paper, we also focus our attention on the immunohistochemical expression of APE1/ Ref-1 (APE1).…”

Section: Introductionmentioning

confidence: 99%

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Londero

Orsaria

Marzinotto

et al. 2016

Histochem Cell Biol

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To evaluate the expression of markers correlated with cellular senescence and DNA damage (8-hydroxy-2′-deoxy-guanosine (8-OHdG), p53, p21, APE1/Ref-1 (APE1), interleukin (IL-6 and IL-8) in placentas from healthy and pathologic pregnancies. This retrospective study considered a placental tissue micro-array containing 92 controls from different gestational ages and 158 pathological cases including preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes,low platelet count), small for gestational age (SGA)fetuses, and intrauterine growth restriction (IUGR) occurringat different gestational ages. In this study, we demonstrated a significant influence of gestational age on the expression in the trophoblast of 8-OHdG, p53, p21, APE1, and IL-6. In placentas of cases affected by PE, HELLP, or IUGR, there was an increased expression of 8-OHdG, p53, APE1, and IL-6 compared to controls (only IL-8 was significantly decreased in cases). In both groups of pathology between 22- and 34-week gestation and after 34-week gestation, APE1 levels were higher in the trophoblast of women affected by hypertensive disorders of pregnancy than women carrying an IUGR fetus. The cytoplasmic expression of 8-OHdG was increased in placentas in IUGR cases compared to PE or HELLP pregnancies. In cases after 34-week gestation, p21 was higher in SGA and IUGR than in controls and late PE. Moreover, p53 was increased after 34-week gestation in IUGR pregnancies. Placentas from pathological pregnancies had an altered expression of\ud 8-OHdG, p53, p21, APE1, IL-6, and IL-8. The alterations of intracellular pathways involving these elements may be the cause or the consequence of placental dysfunction, but in any case reflect an impaired placental function, possibly due to increased aging velocity in pathologic cases

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“…After washing, the bound proteins were resolved by SDS-PAGE, and visualized by ammoniacal silver staining according to Shevchenko's protocol (Shevchenko et al 1996). For identification, protein bands were excised from the gel, triturated, in-gel S-alkylated and digested with trypsin as previously reported (Caratu et al 2007, Vascotto et al 2007. Gel particles were extracted with 25 mM NH 4 HCO 3 /acetonitrile (1:1 v/v) by sonication.…”

Section: Reporter Constructs and Expression Plasmidsmentioning

confidence: 99%

“…Peptide mixtures were loaded on the MALDI target together with a-cyano-4-hydroxycinnamic acid as matrix, using the dried droplet technique. Samples were analyzed with a Voyager-DE PRO spectrometer (Applera, Foster City, CA, USA; Caratu et al 2007, Vascotto et al 2007. Mass spectra were acquired in reflectron mode; internal mass calibration was performed with peptides from trypsin autoproteolysis.…”

Section: Reporter Constructs and Expression Plasmidsmentioning

confidence: 99%

Poly(ADP-ribose) polymerase 1 binds to Pax8 and inhibits its transcriptional activity

Palma

Cristofaro²,

D’Ambrosio³

et al. 2008

Journal of Molecular Endocrinology

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Pax8 is a transcription factor that plays an important role in the regulation of genes that are exclusively expressed in differentiated thyroid cells. In the thyroid cell environment, evidence exists that Pax8 is part of a multiprotein complex in which its transcriptional activity may be modulated by specific co-factors. In an attempt to identify proteins that interact with Pax8, we performed pull-down experiments challenging the GST-Pax8 fusion protein with protein extracts prepared from the thyroid differentiated cell line PC Cl3. By this approach, we isolated a 113-kDa protein that is able to associate with Pax8, which was further identified by mass fingerprint experiments as poly(ADP-ribose) polymerase 1 (PARP1). To further confirm this interaction, we also showed that PARP1 can be co-immunoprecipitated with Pax8 in vivo from a thyroid cell extract. Gel shifts experiments demonstrated that PARP1 binding to Pax8 significantly inhibits Pax8 binding to DNA. Accordingly, we provide evidence that the functional outcome of such an interaction is a significant downregulation of Pax8 transcriptional activity. In the context of thyroid-specific gene transcription, our results suggest that PARP1 behaves as an important negative co-factor involved in the regulation of Pax8-dependent gene expression.

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Oxidized Transthyretin in Amniotic Fluid as an Early Marker of Preeclampsia

Cited by 69 publications

References 42 publications

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia

Placental aging and oxidation damage in a tissue micro-array model: an immunohistochemistry study

Poly(ADP-ribose) polymerase 1 binds to Pax8 and inhibits its transcriptional activity

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