Immunoregulatory Factors Secreted by Human or Murine Placenta or Gestational Tumors
Gérard Chaouat in The Immunology of the Fetus, 2020
Early pregnancy factor (EPF) has been reported to inhibit a variety of tests. Originally, it was demonstrated by the Rosette Inhibition Test17 of which the significance and reproducibility are quite doubtful18 (claims have been made that it could suppress DTH in mice by a cascade of Tsf induction). In parallel, suppressor inducer factors (of labile nature) were reported in the supernatants of murine blastocysts,19 whose biochemistry was hampered by continuous degradation. EPF is reportedly purified to homogeneity, although, strangely enough for a molecule of such biological importance, no sequence is (yet) available. It is reported to be a mixture of 250,000-, 50,000-, and 20,000-Da molecules in sheep; 180,000 and 40,000 Da in mice; 800,000, 300,000, and 74,000 Da, with peaks occurring also at 370,000, 600,000, and 140,000 Da in humans.20 Thus, the nature of EPF is still itself a matter of debate.
Fertilization and normal embryonic and early fetal development
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
At the time when blastocyst is prepared for implantation, in the middle of the luteal phase of cycle, endometrium is about 10 to 14mm thick. It is prepared for the implantation by various factors: EGF, IGF-I, and local paracrine and autocrine factors. From day 16 to 22, the receptivity of the endometrium is the highest, which is called “implantation window.” At that time, a large number of pinopodes (outgrowth of cytoplasm of endometrial cells) occur, and help blastocyst to implant. When zona pellucida disappears, it makes it possible for conceptus to make contact with decidual endometrium. Implantation consists of three phases: apposition, adhesion, and invasion. Apposition and adhesion are assisted with adhesive molecules of endometrium like laminin, fibronectin, and receptors like integrins. Conceptus produces signals that make change in mother’s blood flow. It produces early pregnancy factor, which has immunosuppressive effect. By the beginning of the implantation, proteases and matrix metalloproteinases are activated. Conceptus that is stuck to the surface of the endometrium begins its invasion. Enzymes of the trophoblast invade mother’s circulation and build hemochorial placentation.
Regulation of the Arachidonic Acid Cascade and PAF Metabolism in Reproductive Tissues
Murray D. Mitchell in Eicosanoids in Reproduction, 2020
PAF is produced not only by the embryo during early pregnancy, but also by the endometrium of the uterus.150 Uterine PAF production is highest just prior to implantation and drops in areas of the uterus adjacent to the embryo at the time of implantation. Thus, the drop in uterine PAF production corresponds with the implantation-associated return of platelets to the peripheral circulation. Administration of PAF antagonists has also been shown to inhibit implantation in rats and mice151,152 and may be inhibiting PAF production by the uterus as well as by the embryo. Consequently, it seems reasonable to speculate that production of PAF by both the embryo and uterus is a necessary prerequisite for successful implantation. The precise role(s) of PAF in the maintenance of early pregnancy has not been established. However, PAF has been shown to induce production of early pregnancy factor (EPF) in mice, a protein normally found in maternal serum only during pregnancy.153 PAF may also be involved in ovulation,154 a process which has been compared to the inflammatory response. The instillation of a PAF antagonist into the ovary of rats reduced the number of ovulations. This action could be reversed by the simultaneous administration of PAF. PAF has also been reported in rabbit spermatozoa;155 however, a role for PAF in sperm physiology is currently unknown.
Hydrogen deuterium exchange mass spectrometry applied to chaperones and chaperone-assisted protein folding
Published in Expert Review of Proteomics, 2019
Florian Georgescauld, Thomas E. Wales, John R. Engen
As described in Section 2 above, analysis of the folding of mitochondrial malate dehydrogenase in the presence of single-ring GroEL was one of the first studies reported in peptide-level HDX MS [33]. A greatly expanded study of maltose binding protein (MBP) by GroEL/GroES was reported by Ye et al. in 2018 [51]. In this newer study, it was clearly shown that MBP, which is not a natural GroEL/GroES substrate, folds differently in the presence of the chaperone than it does when it is by itself. MBP is a periplasmic monomer of 42.5 kDa, involved in the catabolism of maltodextrins. It has low intrinsic aggregation propensity and because the folding of some mutants can significantly be accelerated by GroEL/GroES, MBP has been used as model for the chaperonin-assisted folding. Ye et al. used HDX MS to characterize the folding pathway of WT-MBP and a folding-defective mutant (V9G) in the absence of GroEL/GroES. Peptides for both proteins showed a bimodal distribution during folding of an early intermediate, indicating that they were either unfolded (heavier form) or folded (lighter form), but not partially folded (Figure 7, upper panels). However, the V9G mutant, which is GroEL/GroES dependent, displayed kinetics for the early intermediate that were approximately 20-fold slower in some parts of the protein (Figure 7, lower panels). When the V9G mutant was allowed to refold with GroEL/GroES, the chaperones restored a WT-like folding pathway. Why GroEL/GroES acts mainly on the early intermediate in the folding of MBP, which is native-like and highly hydrophobic, remains to be discovered.
Chaperonomics in leptospirosis
Published in Expert Review of Proteomics, 2018
Arada Vinaiphat, Visith Thongboonkerd
Subsequently, the differentially identified OMPs from proteomic analysis were compared to the transcriptional differences reported in their own previous microarray study [95,98]. Comparison of proteomic and transcriptomic data showed correlation of changes in protein and transcript levels for only some HSPs. A specific set of upregulated HSPs, namely DnaK and GroEL, identified by proteomic analysis showed no change in their expression at the mRNA level [98]. In contrast to the aforementioned studies, global proteome analysis of L. interrogans serovar Copenhageni grown in the presence of serum under iron limitation compared to the conventional culture condition revealed downregulation of several chaperone proteins, including IbpA-1, GroES, and ClpA-1 [100]. The contradictory changes in expression of HSPs suggest that the pathogenic L. interrogans undergoes differential adaptive responses at both transcriptional and translational levels in different environmental conditions.
Functional analysis and cryo-electron microscopy of Campylobacter jejuni serine protease HtrA
Published in Gut Microbes, 2020
Urszula Zarzecka, Alessandro Grinzato, Eaazhisai Kandiah, Dominik Cysewski, Paola Berto, Joanna Skorko-Glonek, Giuseppe Zanotti, Steffen Backert
All bacteria have effective stress responses to limit protein damage under harsh environmental conditions. In addition to the common cytoplasmic stress response proteins (DnaK, GroES/EL, GrpE, DnaJ, ClpB, etc.),19,20 the HtrA (high-temperature requirement A) protein plays an important protective function in the cellular envelope. This protein exhibits both protease and chaperone activities and is found in almost all bacteria.21 The best-characterized member of this protein family is HtrA from Escherichia coli (HtrAEc, also known as DegP).22,23 As a protein quality control factor, DegP recognizes and degrades proteins that are not properly folded. In particular, DegP preferentially digests unfolded polypeptides with exposed hydrophobic residues and it mainly hydrolyzes peptide bonds after hydrophobic amino acid residues.24 A characteristic feature of the HtrA family of proteins is the presence of a chymotrypsin-type protease domain as well as one or two C-terminal PDZ domains (Postsynaptic density protein 95, Drosophila disc large tumor suppressor and Zonula occludens-1 protein domain).25 PDZ domains are typically involved in substrate binding, regulation of the proteolytic activity and inter-subunitinteractions.26
Related Knowledge Centers
- Chaperonin
- Escherichia Coli
- Groel
- Oligomer
- Protein
- Protein Folding
- Protein Secondary Structure
- Protein Subunit
- Gene
- Molecular Binding