scholarly journals Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity

Toxics ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 290
Author(s):  
Jith Thomas ◽  
Errol M. Thomson
Keyword(s):  
Stress Hormones ◽  
Differential Susceptibility ◽  
Strain Differences ◽  
High Specificity ◽  
Tissue Level ◽  
Intercellular Adhesion Molecule ◽  
Stress Axis ◽  
Mrna Levels ◽  
Regulatory Factors ◽  
Glucocorticoid Metabolism

Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O3) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic–pituitary–adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O3 for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O3 exposure. Ozone reduced the ratio of 11β-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O3 in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O3-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O3 are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O3. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility.

scholarly journals Prenatally traumatized mice reveal hippocampal methylation and expression changes of the stress-related genes Crhr1 and Fkbp5

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  
Keyword(s):  
Stress Reactivity ◽  
Dorsal Hippocampus ◽  
Methylation Status ◽  
Stress Axis ◽  
Mrna Levels ◽  
Fk506 Binding Protein ◽  
Adult Mice ◽  
Stress Related Genes ◽  
Long Term Impact

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.

scholarly journals Corticosteroid receptors involved in stress regulation in common carp, Cyprinus carpio

2008 ◽  
Vol 198 (2) ◽  
pp. 403-417 ◽  
Author(s):  
Ellen H Stolte ◽  
Aurélia F de Mazon ◽  
Karen M Leon-Koosterziel ◽  
Maria Jesiak ◽  
Nic R Bury ◽  
...  
Keyword(s):  
Common Carp ◽  
Cyprinus Carpio ◽  
Bioinformatic Analysis ◽  
Duplication Event ◽  
Stress Axis ◽  
Mrna Levels ◽  
Stress Regulation ◽  
Regulatory Processes ◽  
The Brain ◽  
Higher Sensitivity

In higher vertebrates, mineralo- (aldosterone) and glucocorticoids (cortisol/corticosterone) exert their multiple actions via specific transcription factors, glucocorticoid (GR) and mineralocorticoid (MR) receptors. Teleostean fishes lack aldosterone and mineral regulatory processes seem under dominant control by cortisol. Despite the absence of the classical mineralocorticoid aldosterone, teleostean fishes do have an MR with cortisol and possibly 11-deoxycorticosterone (DOC) (as alternative for aldosterone) as predominant ligands. We studied corticoid receptors in common carp (Cyprinus carpio L). Through homology cloning and bioinformatic analysis, we found duplicated GR genes and a single MR gene. The GR genes likely result from a major genomic duplication event in the teleostean lineage; we propose that the gene for a second MR was lost. Transactivation studies show that the carp GRs and MR have comparable affinity for cortisol; the MR has significantly higher sensitivity to DOC, and this favours a role for DOC as MR ligand in fish physiology. mRNA of the GRs and the MR is expressed in forebrain (in pallial areas homologous to mammalian hippocampus), corticotrophin-releasing hormone (CRH) cells in the pre-optic nucleus (NPO) and pituitary pars distalis ACTH cells, three key neural/endocrine components of the stress axis. After exposure to prolonged and strong (not to mild acute) stressors, mRNA levels of both GRs and MR become down-regulated in the brain, but not in the NPO CRH cells or pituitary ACTH cells. Our data predicts a function in stress physiology for all CRs and suggest telencephalon as a first line cortisol target in stress.

Expression of the Saccharomyces cerevisiae GAL7 gene on autonomous plasmids

1984 ◽  
Vol 4 (10) ◽  
pp. 2062-2071
Author(s):  
S M Baker ◽  
P G Okkema ◽  
J A Jaehning
Keyword(s):  
Gene Dosage ◽  
Constitutive Expression ◽  
Single Copy ◽  
Initial Time ◽  
Sufficient Information ◽  
Mrna Levels ◽  
Dna Encoding ◽  
Yeast Plasmid ◽  
Regulatory Factors

We used a combination of cloned DNA fragments encoding the GAL7 gene, yeast plasmid vectors, and chromosomal gal7 deletions to characterize the in vivo transcription of the GAL7 gene on autonomously replicating plasmids. Our results demonstrated that a plasmid-borne 3.1-kilobase DNA fragment containing the GAL7 gene provides sufficient information to mimic the regulated expression of the chromosomal location. Normal expression of GAL7 could occur in the absence of DNA encoding the functional genes of the GAL cluster region and was not altered when the gene was adjacent to other plasmid elements such as autonomously replicating sequences or centromeres. The chromosomal and single-copy centromeric plasmid locations of GAL7 were indistinguishable in their response to growth conditions (induction by galactose, repression by glucose) and positive and negative regulatory factors (GAL4 and GAL80). Increasing the gene dosage to more than 200 copies per cell resulted in constitutive expression of the GAL7 mRNA; fully induced mRNA levels were increased more than 10-fold at these high gene dosages. When cells were shifted from noninducing to inducing conditions, the initial time of appearance and the rate of accumulation of GAL7 mRNA were altered in cell populations containing multiple GAL7 genes. The induction kinetics and final accumulation of the chromosomal GAL10 mRNA were also affected by the presence of multiple copies of the GAL7 gene; these results are consistent with a model involving limiting amounts of regulatory factors.

scholarly journals Characterization of the Crithidia fasciculata mRNA Cycling Sequence Binding Proteins

2001 ◽  
Vol 21 (14) ◽  
pp. 4453-4459 ◽  
Author(s):  
Riaz Mahmood ◽  
Bidyottam Mittra ◽  
Jane C. Hines ◽  
Dan S. Ray
Keyword(s):  
Cell Cycle ◽  
Protein Complexes ◽  
Coiled Coil ◽  
High Specificity ◽  
Binding Activity ◽  
Mrna Levels ◽  
Crithidia Fasciculata ◽  
Cysteine Motif ◽  
Cell Extracts ◽  
Sequence Elements

ABSTRACT The Crithidia fasciculata cycling sequence binding protein (CSBP) binds with high specificity to sequence elements in several mRNAs that accumulate periodically during the cell cycle. Mutations in these sequence elements abolish both cycling of the mRNA and binding of CSBP. Two genes, CSBPA andCSBPB, encoding putative subunits of CSBP have been cloned and were found to be present in tandem on the same DNA molecule and to be closely related. CSBPA andCSBPB are predicted to encode proteins with sizes of 35.6 and 42.0 kDa, respectively. Both CSBPA and CSBPB proteins have a predicted coiled-coil domain near the N terminus and a novel histidine and cysteine motif near the C terminus. The latter motif is conserved in other trypanosomatid species. Gel sieving chromatography and glycerol gradient sedimentation results indicate that CSBP has a molecular mass in excess of 200 kDa and an extended structure. Recombinant CSBPA and CSBPB also bind specifically to the cycling sequence and together can be reconstituted to give an RNA gel shift similar to that of purified CSBP. Proteins in cell extracts bind to an RNA probe containing six copies of the cycling sequence. The RNA-protein complexes contain both CSBPA and CSBPB, and the binding activity cycles in near synchrony with target mRNA levels.CSBPA and CSBPB mRNA and protein levels show little variation throughout the cell cycle, suggesting that additional factors are involved in the cyclic binding to the cycling sequence elements.

scholarly journals The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA / Plejotropni Efekti Atorvastatina Kod Pacijenata Sa Stabilnom Anginom: Dokazi Dobijeni Analizom Veličine I Raspodele Subfrakcija Lipoproteina Velike Gustine I Plazmatske mRna

2015 ◽  
Vol 34 (3) ◽  
pp. 314-322 ◽  
Author(s):  
Bosa Mirjanić-Azarić ◽  
Zorana Jelić-Ivanović ◽  
Aleksandra Zeljković ◽  
Jelena Vekić ◽  
Günther Jürgens ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Stable Angina ◽  
Intercellular Adhesion ◽  
Pleiotropic Effects ◽  
Intercellular Adhesion Molecule ◽  
Cathepsin S ◽  
Mrna Levels ◽  
Intercellular Adhesion Molecule 1 ◽  
Group A ◽  
Group B

SummaryBackground: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B).Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses.Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p=0.023) and significantly increased after therapy.Conclusion: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy

Selective induction of intercellular adhesion molecule-1 by interferon-gamma in human airway epithelial cells

1992 ◽  
Vol 263 (1) ◽  
pp. L79-L87 ◽  
Author(s):  
D. C. Look ◽  
S. R. Rapp ◽  
B. T. Keller ◽  
M. J. Holtzman
Keyword(s):  
Epithelial Cells ◽  
Interferon Gamma ◽  
Adhesion Molecule ◽  
Airway Epithelial Cells ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Intercellular Adhesion Molecule 1 ◽  
Ifn Gamma

To evaluate the factors controlling migration of leukocytes into pulmonary airway epithelium, we determined the biochemical mechanisms responsible for the regulation of intercellular adhesion molecule-1 (ICAM-1) expression on cultured monolayers of human tracheal epithelial cells (HTECs) or SV40 virus-transformed human bronchial epithelial cells (BEAS-2B). Validation experiments with human umbilical vein endothelial cells (HUVECs) demonstrated little detectable ICAM-1 expression on unstimulated cells or on cells incubated with interferon-gamma (IFN-gamma), but HUVEC monolayers responded to interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) with significant increases in ICAM-1 and ICAM-1-dependent adherence of polymorphonuclear leukocytes (PMNs). HTEC monolayers also exhibited no significant basal ICAM-1 expression but, in contrast to HUVEC monolayers, had marked increases in ICAM-1 expression and ICAM-1-dependent PMN adherence only after incubation with IFN-gamma (and not after IL-1 beta or TNF-alpha) treatment. BEAS-2B cells also exhibited relatively selective IFN-gamma stimulation of ICAM-1 expression and ICAM-1-dependent PMN adherence but (like late passage HTEC) showed significant basal ICAM-1 expression. Differences in IFN-gamma effect on ICAM-1 levels between HUVEC and HTEC monolayers were not due to differences in number or responsiveness of IFN-gamma receptors, because both cell types exhibited a similar number of receptors and other IFN-gamma-dependent responses of HUVECs remained active. In all analyses, ICAM-1 mRNA levels correlated closely with detection of ICAM-1 on the cell surface.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Presence of a Poly(A) Binding Protein and Two Proteins with Cell Cycle-Dependent Phosphorylation in Crithidia fasciculata mRNA Cycling Sequence Binding Protein II

2004 ◽  
Vol 3 (5) ◽  
pp. 1185-1197 ◽  
Author(s):  
Bidyottam Mittra ◽  
Dan S. Ray
Keyword(s):  
Cell Cycle ◽  
Binding Protein ◽  
High Specificity ◽  
Binding Activity ◽  
Mrna Levels ◽  
Crithidia Fasciculata ◽  
Target Mrna ◽  
Cycle Dependent

ABSTRACT Crithidia fasciculata cycling sequence binding proteins (CSBP) have been shown to bind with high specificity to sequence elements present in several mRNAs that accumulate periodically during the cell cycle. The first described CSBP has subunits of 35.6 (CSBPA) and 42 kDa (CSBPB). A second distinct binding protein termed CSBP II has been purified from CSBPA null mutant cells, lacking both CSBPA and CSBPB proteins, and contains three major polypeptides with predicted molecular masses of 63, 44.5, and 33 kDa. Polypeptides of identical size were radiolabeled in UV cross-linking assays performed with purified CSBP II and 32P-labeled RNA probes containing six copies of the cycling sequence. The CSBP II binding activity was found to cycle in parallel with target mRNA levels during progression through the cell cycle. We have cloned genes encoding these three CSBP II proteins, termed RBP63, RBP45, and RBP33, and characterized their binding properties. The RBP63 protein is a member of the poly(A) binding protein family. Homologs of RBP45 and RBP33 proteins were found only among the kinetoplastids. Both RBP45 and RBP33 proteins and their homologs have a conserved carboxy-terminal half that contains a PSP1-like domain. All three CSBP II proteins show specificity for binding the wild-type cycling sequence in vitro. RBP45 and RBP33 are phosphoproteins, and RBP45 has been found to bind in vivo specifically to target mRNA containing cycling sequences. The levels of phosphorylation of both RBP45 and RBP33 were found to cycle during the cell cycle.

scholarly journals Mouse Cyp4a isoforms: enzymatic properties, gender- and strain-specific expression, and role in renal 20-hydroxyeicosatetraenoic acid formation

2007 ◽  
Vol 403 (1) ◽  
pp. 109-118 ◽  
Author(s):  
Dominik N. Muller ◽  
Cosima Schmidt ◽  
Eduardo Barbosa-Sicard ◽  
Maren Wellner ◽  
Volkmar Gross ◽  
...  
Keyword(s):  
Target Organ Damage ◽  
Strain Differences ◽  
Organ Damage ◽  
Mouse Kidney ◽  
Mrna Levels ◽  
Hydroxyeicosatetraenoic Acid ◽  
Recombinant Enzymes ◽  
Specific Expression ◽  
Protein Levels ◽  
Acid Hydroxylation

AA (arachidonic acid) hydroxylation to 20-HETE (20-hydroxyeicosatetraenoic acid) influences renal vascular and tubular function. To identify the CYP (cytochrome P450) isoforms catalysing this reaction in the mouse kidney, we analysed the substrate specificity of Cyp4a10, 4a12a, 4a12b and 4a14 and determined sex- and strain-specific expressions. All recombinant enzymes showed high lauric acid hydroxylase activities. Cyp4a12a and Cyp4a12b efficiently hydroxylated AA to 20-HETE with Vmax values of approx. 10 nmol·nmol−1·min−1 and Km values of 20–40 μM. 20-Carboxyeicosatetraenoic acid occurred as a secondary metabolite. AA hydroxylase activities were approx. 25–75-fold lower with Cyp4a10 and not detectable with Cyp4a14. Cyp4a12a and Cyp4a12b also efficiently converted EPA (eicosapentaenoic acid) into 19/20-OH- and 17,18-epoxy-EPA. In male mice, renal microsomal AA hydroxylase activities ranged between approx. 100 (NMRI), 45–55 (FVB/N, 129 Sv/J and Balb/c) and 25 pmol·min−1·mg−1 (C57BL/6). The activities correlated with differences in Cyp4a12a protein and mRNA levels. Treatment with 5α-dihydrotestosterone induced both 20-HETE production and Cyp4a12a expression more than 4-fold in male C57BL/6 mice. All female mice showed low AA hydroxylase activities (15–25 pmol·min−1·mg−1) and very low Cyp4a12a mRNA and protein levels, but high Cyp4a10 and Cyp4a14 expression. Renal Cyp4a12b mRNA expression was almost undetectable in both sexes of all strains. Thus Cyp4a12a is the predominant 20-HETE synthase in the mouse kidney. Cyp4a12a expression determines the sex- and strain-specific differences in 20-HETE generation and may explain sex and strain differences in the susceptibility to hypertension and target organ damage.

scholarly journals Unexplained habitual abortion is associated with a reduced endometrial release of soluble intercellular adhesion molecule-1 in the luteal phase of the cycle

2000 ◽  
pp. 477-480 ◽  
Author(s):  
B Gaffuri ◽  
L Airoldi ◽  
AM Di Blasio ◽  
P Vigano ◽  
AM Miragoli ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Stromal Cells ◽  
Luteal Phase ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Soluble Form ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Endometrial Stromal Cells ◽  
History Of

Although the mechanisms causing recurrent spontaneous abortion (RSA) remain frequently speculative, recent evidence indicates that a specific uterine immune-endocrine network plays a pivotal role in the continuation of pregnancy. We have recently demonstrated that an adhesion molecule of the immune system, named intercellular adhesion molecule (ICAM)-1, is markedly expressed at both protein and mRNA levels in endometrial stromal cells and is able to mediate their interaction with lymphoid cells. Moreover, we have shown that the soluble form of ICAM-1 (sICAM-1) can be released by the endometrium in a hormone-dependent manner. The present study was designed to determine whether surface and/or sICAM-1 expression by cultured endometrial stromal cells could be related to early pregnancy loss in patients with a history of unexplained RSA. Luteal-phase endometrial biopsies were obtained from eight patients who had experienced three or more consecutive unexplained RSAs in the first trimester and 12 control fertile women. Surface ICAM-1 was similarly expressed on luteal-phase endometrial cells obtained from women with and without a history of unexplained RSA. In contrast, the endometrial release of sICAM-1 was significantly lower in abortion-prone patients than in control women. sICAM-1 is a cytokine-inducible molecule able to interfere with several immunological responses and the reduced levels of the protein shed by the endometrium in patients who have suffered from unexplained RSAs may reflect the presence of an altered immunological environment during the early phases of pregnancy.

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