Pre‐translational regulation by glucocorticoid of fatty acid and phosphatidylcholine synthesis in type II cells from fetal rat lung

Batenburg, Joseph J.; Elfring, R. H.

doi:10.1016/0014-5793(92)80759-a

Cited by 24 publications

(12 citation statements)

References 33 publications

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“…Although the hormone produced an increase in CT mRNA in these studies, these effects appeared to be relatively small and were not associated with an increase in immunoreactive CT. The increase in CT message by betamethasone observed using our methods, however, is consistent with prior results in fetal lung explant culture where glucocorticoids also appear to exert modest pretranslational effects on CT mRNA [52,53]. On the basis of these results, we cannot exclude the possibility that the hormone may have altered either the translational efficiency of CT mRNA or the degradation of enzyme protein in lung tissues.…”

Section: Discussionsupporting

confidence: 89%

Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung

Mallampalli

Mathur

Warnock

et al. 1996

Biochemical Journal

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Glucocorticoids appear to play an integral role in stimulating surfactant synthesis by activating the rate-regulatory enzyme for phosphatidylcholine synthesis, CTP:cholinephosphate cytidylyltransferase (CT). The activity of liver CT, in vitro, has been shown to be inhibited by the sphingomyelin hydrolysis product, sphingosine. In order to investigate the mechanisms by which glucocorticoids alter CT activity, in vivo, we administered betamethasone (1 mg/kg intraperitoneally) sequentially to adult male rats for 5 days. Betamethasone increased CT activity 2-fold relative to control in whole lung. The hormone also increased membrane-bound activity, but did not affect cytosolic enzyme activity. Betamethasone modestly increased CT mRNA as determined by the reverse-transcription PCR and Southern analysis of PCR products, but did not alter the levels of immunoreactive enzyme in lung membranes as demonstrated by Western blotting. The hormone did, however, produce a nearly 3-fold increase in membrane-associated sphingomyelin, and co-ordinately a substantial decrease in the levels of sphingosine in lung membranes. Sphingosine, but not sphinganine, was a competitive, reversible inhibitor of lung CT with respect to the enzyme activator, phosphatidylglycerol. Betamethasone decreased the activities of the sphingomyelin hydrolases: acid sphingomyelinase by 33% and of alkaline ceramidase by 21%. The hormone also inhibited the generation of sphingosine from lysosphingomyelin in lung membranes. There was no significant effect of the hormone on serine palmitoyltransferase activity, the first committed enzyme for sphingolipid biosynthesis. Further, administration of L-cycloserine, an inhibitor of sphingosine formation, was shown to stimulate CT activity by 74% and increase disaturated phosphatidylcholine in alveolar lavage by 52% relative to control. These observations suggest that glucocorticoids up-regulate surfactant synthesis at the level of a key regulatory enzyme by significantly altering the availability of inhibitory metabolites resulting from sphingomyelin hydrolysis.

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Section: Discussionsupporting

confidence: 89%

Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung

Mallampalli

Mathur

Warnock

et al. 1996

Biochemical Journal

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“…The actions of glucocorticoids are mediated by the glucocorticoid receptor ␣ and ␤ (GR␣, GR␤) present on target cells (115,192). The effects of glucocorticoids on maturation of surfactant biosynthesis by fetal type II cells are dependent on mesenchymal cells, which are likely to provide paracrine signals inducing epithelial maturation (11,217). In mice, deletion of GR␣ delays lung maturation causing respiratory distress at birth (43).…”

Section: B Glucocorticoid Receptors and Perinatal Lung Maturationmentioning

confidence: 99%

Transcriptional Control of Lung Morphogenesis

Maeda

Davé²,

Whitsett³

2007

Physiological Reviews

433

387

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The vertebrate lung consists of multiple cell types that are derived primarily from endodermal and mesodermal compartments of the early embryo. The process of pulmonary organogenesis requires the generation of precise signaling centers that are linked to transcriptional programs that, in turn, regulate cell numbers, differentiation, and behavior, as branching morphogenesis and alveolarization proceed. This review summarizes knowledge regarding the expression and proposed roles of transcription factors influencing lung formation and function with particular focus on knowledge derived from the study of the mouse. A group of transcription factors active in the endodermally derived cells of the developing lung tubules, including thyroid transcription factor-1 (TTF-1), β-catenin, Forkhead orthologs (FOX), GATA, SOX, and ETS family members are required for normal lung morphogenesis and function. In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop. Lung formation is dependent on reciprocal signaling among cells of both endodermal and mesenchymal compartments that instruct transcriptional processes mediating lung formation and adaptation to breathing after birth.

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“…Surfactant apoprotein production is deficient in ARDS, presumably resulting from damage to type II alveolar epithelial cells. Furthermore, the ARDS patients in the present study received glucocorticoids, that are known to affect surfactant production and secretion [23]. These may be possible explanations for the absence of a significant relationship between the SP-A concentration and the clinical features of ARDS, and also for the decreased SP-A concentrations in the samples of aspirated secretion and sputum samples from ARDS patients compared to those from patients with cardiogenic pulmonary oedema.…”

Section: Discussionmentioning

confidence: 84%

Surfactant apoprotein-A concentration in airway secretions for the detection of pulmonary oedema

Shimura

Masuda²,

Takishima³

et al. 1996

Eur Respir J

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S Su ur rf fa ac ct ta an nt t a ap po op pr ro ot te ei in n--A A c co on nc ce en nt tr ra at ti io on n i in n a ai ir rw wa ay y s se ec cr re et ti io on ns s f fo or r t th he e d de et te ec ct ti io on n o of f p pu ul lm mo on na ar ry y o oe ed de em ma a ABSTRACT: Patients with cardiogenic pulmonary oedema expectorate foamy sputum containing surfactant, which might be expected to include surfactant apoprotein A (SP-A). SP-A is specific for lung surfactant. We have measured the SP-A concentration in airway secretions to determine whether it is useful in distinguishing pulmonary oedema from other disorders. Samples of sputum and of aspirated airway secretion were obtained from 11 patients with cardiogenic pulmonary oedema, seven patients with clinically stable congestive heart failure, five patients with adult respiratory distress syndrome (ARDS) and 20 control patients (10 intubated) with other respiratory diseases. The samples were used for the measurement of SP-A concentration by a two-site simultaneous immunoassay with monoclonal antibodies against SP-A.SP-A concentrations, measured in samples of sputum and aspirated secretions, depended on the diagnosis of the patients from which they had come. In descending order these samples came from patients with: cardiogenic pulmonary oedema (1324±197 µg·mL -1 ; n=33); ARDS (311±47 µg·mL -1 ; n=23); clinically stable congestive heart failure (78±10 µg·mL -1 ; n=21); and control conditions (3.0±0.6 µg·mL -1 ; n=30). Concentrations from disease samples did not overlap with controls. In samples from patients with cardiogenic pulmonary oedema, the SP-A concentration correlated with mean pulmonary capillary wedge pressure (PCWP) (p<0.001; n=39).These findings indicate that the measurement of the surfactant apoprotein A concentration in airway secretions may be useful for the detection of pulmonary oedema.

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Pre‐translational regulation by glucocorticoid of fatty acid and phosphatidylcholine synthesis in type II cells from fetal rat lung

Cited by 24 publications

References 33 publications

Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung

Betamethasone modulation of sphingomyelin hydrolysis up-regulates CTP:cholinephosphate cytidylyltransferase activity in adult rat lung

Transcriptional Control of Lung Morphogenesis

Surfactant apoprotein-A concentration in airway secretions for the detection of pulmonary oedema

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