ABSTRACT
BACKGROUND: Pregnancy during lactation is common in Egypt and is often unplanned. Overlap between pregnancy and lactation could be associated with an increased risk for the pregnant mother, her fetus as well as her nursing child. AIM OF THE STUDY: The current study aims to compare the maternal and perinatal outcome of pregnancies occurred during lactation with those occurred after weaning in women with substandard nutrition. MATERIALS AND METHODS: A prospective-cohort study was carried out in six Maternal and Child Health Centers in Assiut-Egypt. Estimated sample size was 540 women divided equally into two groups; the first included women who got pregnant during breastfeeding (PDBF), while the second included women who got pregnant after weaning (PAW). Tools were consisted of structured interview questionnaire including personal history, obstetrical data, breastfeeding, family planning histories and dietary intake during pregnancy. Pregnant women had been followed up to delivery to assess different maternal and fetal outcomes. RESULTS: Miscarriage rate was not statistically significant between both groups (2.2% in PDBF and 0.4% in PAW, p = 0.284). Women in PDBF group had higher prevalence of maternal anemia (54.1% versus 30.7%), intrauterine growth restriction (16.7% versus 4.8%), cesarean delivery (43.7% versus 31.5%), prolonged labor (13.3% versus 11.1%) and low birth weight infants (15.7% versus 8.8%) compared to women in PAW group. CONCLUSION: Pregnancy during breastfeeding is associated with an increase in the overall complications of pregnancy as compared to PAW. Although it does not increase the miscarriage rate, it increases the prevalence of maternal anemia, delayed fetal growth, prolonged labor, cesarean section delivery and the prevalence of low birth weight infants.
ABSTRACT
Dimerization of leucine zipper-containing proteins has been associated characteristically with the formation of a coiled-coil structure between two compatible leucine zipper motifs. In the present study we demonstrate the association of the leucine zipper of cAMP response element-binding protein (CREB) with a zinc finger motif of ATF-2. The association of the CREB leucine zipper with the ATF-2 zinc finger is stabilized if the ATF-2 leucine zipper is intact, implying that the preferred interactive structure of ATF-2 juxtaposes the amino-terminal zinc finger motif of this protein with the carboxy-terminal leucine zipper of this same protein. Furthermore, we demonstrate that the association of the CREB leucine zipper with the ATF-2 zinc finger in vitro blocks the association of the adenoviral E1a protein with ATF-2. Similarly, overexpression of full-length CREB, or a truncated version of this protein corresponding to the carboxy-terminal 74 amino acids that make up the DNA-binding and dimerization domains, can block the ATF-2-mediated transcriptional stimulation by E1a in vivo. Mutation of the ATF-2 zinc finger motif stimulates DNA binding of this protein, and abolishes interactions with E1a and CREB proteins. These results demonstrate that the structural conformation of ATF-2 is critical for DNA binding and protein-protein interactions and, further, that leucine zippers can mediate protein-protein interactions with structural motifs other than leucine zippers.
Subject(s)
Adenovirus E1A Proteins/metabolism , Blood Proteins/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Leucine Zippers , Transcription Factors/metabolism , Activating Transcription Factors , Adenovirus E1A Proteins/genetics , Base Sequence , Blood Proteins/chemistry , Cyclic AMP Response Element-Binding Protein/chemistry , DNA/metabolism , HeLa Cells , Humans , Molecular Sequence Data , Mutation , Protein Conformation , Proto-Oncogene Proteins c-fos/metabolism , Proto-Oncogene Proteins c-jun/metabolism , Transcription Factors/chemistry , Transcriptional Activation , Zinc/metabolismABSTRACT
Recent studies have detailed the ability of activating transcription factor-2 (ATF-2) to mediate adenoviral E1a stimulation of gene expression; however, an endogenous regulator for the transcriptional activity of this protein has not been described. To characterize the regulation of ATF-2 activity, we have expressed full-length and truncated peptides corresponding to various regions of the ATF-2 protein in bacteria and the baculovirus insect cell system. Bacterially expressed truncated (350-505) but not full-length ATF-2, was able to bind a consensus cAMP response element-containing oligonucleotide, suggesting the N-terminal moiety may serve as a negative regulator of DNA-binding activity. In contrast, the full-length ATF-2 protein expressed in Spodoptera frugiperda (Sf9) cells using a recombinant baculovirus was fully competent to bind DNA. Protein phosphatase 2A reversed the DNA-binding activity by dephosphorylating the ATF-2 polypeptide. Microtubule-associated protein kinase catalyzed the phosphorylation and stimulated the DNA-binding activity of bacterially expressed full-length ATF-2. Phosphopeptide mapping of phosphorylated ATF-2 proteins identified a single peptide in the N-terminal moiety of ATF-2 phosphorylated by p42 or p54 microtubule-associated protein kinase. Therefore, we propose that phosphorylation of this regulatory site is sufficient to induce an allosteric structural change in the ATF-2 protein, which allows dimerization and subsequent DNA binding.
