Nuclear factor-κB, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect.

Among the characteristics acquired by many tumour cells is a shift from using oxidative phosphorylation to using glycolysis for ATP production. Although the nuclear factor (NF)-κB family of transcriptional regulators have important roles in tumorigenesis, their ability to function as regulators of metabolism has only been recently investigated. This has revealed the importance of crosstalk between NF-κB, the p53 tumour suppressor and other crucial cell signalling pathways.

p53-dependent regulation of mitochondrial energy production by the RelA subunit of NF-κB.

Aberrant activity of the nuclear factor kappaB (NF-κB) transcription factor family, which regulates cellular responses to stress and infection, is associated with many human cancers. In this study, we define a function of NF-κB in regulation of cellular respiration that is dependent upon the tumor suppressor p53. Translocation of the NF-κB family member RelA to mitochondria was inhibited by p53 by blocking an essential interaction with the HSP Mortalin.

The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration.

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela(-/-) mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function.

Expression of glucocorticoid receptor messenger ribonucleic acid transcripts in the human placenta at term.

Context: Differential promoter use and alternative splicing generate a variety of glucocorticoid receptor (GR) mRNA transcripts, potentially altering the cortisol responsiveness of gestational tissues during pregnancy and labor.

Objective: We examined GR mRNA transcript expression in term placentae before and after labor, in association with fetal sex and after glucocorticoid treatment.

Design: RNA from 34 placentae and from eight placental explants incubated with glucocorticoids were analyzed for the GR mRNA variants GR-alpha, GR-beta, GR-P, and GR-gamma and the untranslated exon one variants 1A1, 1A2, 1A3, 1B, and 1C by quantitative RT-PCR.

Mechanisms regulating prostaglandin H2 synthase-2 mRNA level in the amnion and chorion during pregnancy.

Increasing prostaglandin H(2) synthase (PGHS)-2 expression in the fetal membranes is implicated in the production of prostaglandins (PGs) that stimulate labour. We have determined the activity of the PGHS-2 gene in the amnion and chorion throughout gestation and defined the contribution of transcriptional and post-transcriptional mechanisms to the increase of PGHS-2 mRNA levels. We also measured PGHS-1 mRNA abundance to assess the participation of the two isoenzymes in fetal membrane PG-production during pregnancy.

Proteomic study of plasma proteins in pregnant women with asthma.

Objective And Background: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins.

Methods: Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips.

The effect of maternal asthma on placental and cord blood protein profiles.

Objective: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles.

Methods: Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors.

Regulation of 15-hydroxyprostaglandin dehydrogenase (PGDH) gene activity, messenger ribonucleic acid processing, and protein abundance in the human chorion in late gestation and labor.

The prostaglandin (PG)-inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (PGDH) is highly expressed in the chorion leave. To assess the involvement of PGDH in the regulation of intrauterine PG levels, we have determined the mechanisms that control chorionic PGDH expression in women at term and preterm labor. PGDH gene activity decreased at term and during normal labor.

The control of prostaglandin endoperoxide H-Synthase-2 expression in the human chorion laeve at term.

Objective: Prostaglandin endoperoxide H synthase-2 (PGHS-2), the key enzyme of prostaglandin biosynthesis in gestational tissues, is expressed in the chorion laeve at term. We have determined the mechanisms that control the level of PGHS-2 mRNA in the chorion membrane in order to assess the significance of chorion-derived prostaglandins in term labor.

Methods: Chorion membranes were collected after elective cesarean delivery (CD, n = 21) and after spontaneous labor (SL, n = 20) at term.

The in vivo control of prostaglandin H synthase-2 messenger ribonucleic acid expression in the human amnion at parturition.

Prostaglandin H synthase-2 (PGHS-2) activity and mRNA rise in the human amnion at late gestation, contributing to the increase in intrauterine PG production crucial for labor and delivery. In the present investigation we have determined the mechanism that controls amniotic PGHS-2 mRNA levels in vivo at term parturition. Amnion membranes were collected after elective cesarean section (n = 20), and after spontaneous labor (n = 20).