RETRACTED: Heat shock protein 27 expression is spatially distributed in human placenta and selectively regulated during preeclampsia

Abdulsid, Akrem; Lyall, Fiona

doi:10.1016/j.jri.2013.09.002

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…However, the role of HSP27 phosphorylation in regulating HIF biology has not been described. In fact, expression of HSP27 and pHSP27 has been found to be higher in placental tissues derived from preeclamptic placentas compared to controls (32) and was shown to have differential spatial distribution within the placenta (25). These data suggest that perhaps increased pHSP27 observed in human preeclampsia may be an adaptive response to the placental ischemia.…”

Section: Discussionmentioning

confidence: 84%

Ouabain inhibits placental sFlt1 production by repressing HSP27‐dependent HIF‐1α pathway

et al. 2014

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Up-regulation of placental soluble fms-like tyrosine kinase 1 (sFlt1) contributes to the pathogenesis of preeclampsia. To evaluate novel upstream pathways that regulate placental sFlt1 production, we screened a library of natural compounds (n=502) in human placental cell lines. Here, we report 3 compounds in the cardiac glycoside family, ouabain, gitoxigenin, and digitoxin, that inhibit placental sFlt1 production at nanomolar concentrations in vitro. We further characterized ouabain and demonstrated that it inhibits sFlt1 mRNA and protein expression in human placental cytotrophoblasts and explant cultures in a dose- and time-dependent manner. Ouabain down-regulated sFlt1 production by inhibiting hypoxia-inducible factor 1 (HIF-1α) protein expression in the placenta. Furthermore, we found that phosphorylation of heat-shock protein 27 (HSP27) was necessary for ouabain to inhibit HIF-1α translation. In a rat model of pregnancy-induced hypertension, ouabain reduced mean arterial pressure and enhanced placental HSP27 phosphorylation without any adverse effects on pups. Further studies are needed to explore the usefulness of targeting HIF-1α/HSP27 pathway in preeclampsia.

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Section: Discussionmentioning

confidence: 84%

Ouabain inhibits placental sFlt1 production by repressing HSP27‐dependent HIF‐1α pathway

et al. 2014

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“…In the first trimesters of pregnancy is mainly of the 27-kD protein; however, this changes to the early stages of labour (37-weeks) reducing the expression of Hsp-27 and increasing the 60 and 70-kD proteins (Figure 1F). 11 The biological significance of eHsp-27 activity during the pregnancy in the absence of cell damage suggests that these proteins are involved in cellular protection by reducing the production of molecules associated with oxidative stress, apoptosis, inflammatory ÁLVAREZ-CABRERA ET AL. | 5749 response 10 regulating trophoblast differentiation and migration 12 ( Figure 1E).…”

Section: Resultsmentioning

confidence: 99%

Secretion of heat shock ‐60, ‐70 kD protein, IL‐1β and TNFα levels in serum of a term normal pregnancy and patients with pre‐eclampsia development

Álvarez‐Cabrera¹,

Barrientos‐Galeana²,

Barrera‐García³

et al. 2018

J Cellular Molecular Medi

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The extracellular heat shock proteins (eHsp) family act as molecular chaperones regulating folding, transporting protein and are associated with immune modulation in different physiological and pathological processes. They have been localized in different gestational tissues and their concentration in amniotic fluid and serum has been determined. In the present study, we proposed to determine the concentration of eHsp‐60, ‐70, IL‐1β and TNFα in the serum of pregnant patients with 34 weeks of gestation with and without clinical evidences of preeclampsia (PE). Our results indicate significant increase of these markers in patients with PE with respect to healthy pregnant patients without active labor. Finally, the concentration of eHsp‐60 and ‐70 correlated positively with the hepatic dysfunction markers uric acid, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) glutamic pyruvic transaminase (GPT), and inflammatory IL‐1β and TNFα response. In conclusion, our results demonstrate a strong associated between Hsp and marker of hepatic dysfunction.

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“…Reactive oxygen species and the oxidant/antioxidant balance can be affected as a result [17]. In keeping with this labour has been reported to be associated with placental alterations in several pathways linked to oxidative stress [18]–[24] Other studies looking at heat shock proteins, Mn-SOD, Cu/Zn-SOD and peroxidation of lipids also show an association between labour and placental oxidative stress [9]–[10], [13].…”

Section: Discussionmentioning

confidence: 79%

Paraoxonase 2 Protein Is Spatially Expressed in the Human Placenta and Selectively Reduced in Labour

et al. 2014

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Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role.

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RETRACTED: Heat shock protein 27 expression is spatially distributed in human placenta and selectively regulated during preeclampsia

Cited by 11 publications

References 20 publications

Ouabain inhibits placental sFlt1 production by repressing HSP27‐dependent HIF‐1α pathway

Ouabain inhibits placental sFlt1 production by repressing HSP27‐dependent HIF‐1α pathway

Secretion of heat shock ‐60, ‐70 kD protein, IL‐1β and TNFα levels in serum of a term normal pregnancy and patients with pre‐eclampsia development

Paraoxonase 2 Protein Is Spatially Expressed in the Human Placenta and Selectively Reduced in Labour

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