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Embryonic Lungs (embryonic + lung)

Distribution by Scientific Domains

Life Sciences	75%

Selected Abstracts

Evidence for cocaine and methylecgonidine stimulation of M2 muscarinic receptors in cultured human embryonic lung cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2001
Yinke Yang
Muscarinic cholinoceptor stimulation leads to an increase in guanylyl cyclase activity and to a decrease in adenylyl cyclase activity. This study examined the effects of cocaine and methylecgonidine (MEG) on muscarinic receptors by measurement of cyclic GMP and cyclic AMP content in cultured human embryonic lung (HEL299) cells which specifically express M2 muscarinic receptors. A concentration-dependent increase in cyclic GMP production was observed in HEL299 cells incubated with carbachol, cocaine, or MEG for 24 h. The increase in cyclic GMP content was 3.6 fold for 1 ,M carbachol (P<0.01), 3.1 fold for 1 ,M cocaine (P<0.01), and 7.8 fold for 1 ,M MEG (P<0.001), respectively. This increase in cyclic GMP content was significantly attenuated or abolished by the muscarinic receptor antagonist atropine or the M2 blocker methoctramine. In contrast, cocaine, MEG, and carbachol produced a significant inhibition of cyclic AMP production in HEL299 cells. Compared to the control, HEL299 cells treated with 1 ,M cocaine decreased cyclic AMP production by 30%. MEG and carbachol at 1 ,M decreased cyclic AMP production by 37 and 38%, respectively. Atropine or methoctramine at 1 or 10 ,M significantly attenuated or abolished the cocaine-induced decrease in cyclic AMP production. However, the antagonists alone had neither an effect on cyclic GMP nor cyclic AMP production. Pretreatment of HEL299 cells with pertussis toxin prevented the cocaine-induced reduction of cyclic AMP production. Western blot analysis showed that HEL299 cells specifically express M2 muscarinic receptors without detectable M1 and M3. Incubation of HEL299 cells with cocaine, carbachol, and atropine did not alter the expression of M2 protein levels. However, the inducible isoform of nitric oxide synthase (iNOS) was induced in the presence of cocaine or carbachol and this induction was significantly attenuated after addition of atropine or methoctramine. The present data show that cocaine and MEG significantly affect cyclic GMP and cyclic AMP production in cultured HEL299 cells. Our results also show that these effects result from the drug-induced stimulation of M2 muscarinic receptors accompanied with no alterations of receptor expression. However, the induction of iNOS by cocaine may result in the increase in cyclic GMP production. British Journal of Pharmacology (2001) 132, 451,460; doi:10.1038/sj.bjp.0703819 [source]

Timeless in lung morphogenesis

DEVELOPMENTAL DYNAMICS, Issue 1 2003
Jing Xiao
Abstract The Clock gene, timeless, regulates circadian rhythm in Drosophila, but its vertebrate homolog is critical to embryonic development. Timeless was shown to be involved in murine urethral bud branching morphogenesis. We generated a polyclonal antibody to mouse TIMELESS (mTIM) and studied its distribution and its potential role during lung development, which also requires branching morphogenesis. In the early mouse embryo, TIM was localized to all organs, especially the neural epithelium. In embryonic day (E) 9.5 embryos, TIM was present in both epithelial and mesenchymal cells at the onset of lung morphogenesis. In E15 embryos, TIM decreased in the mesenchyme but remained pronounced in the epithelium of both large and small airways. Later, TIM was localized to a specific subset of epithelial cells with alveolar type 2 phenotype. This finding was verified by immunostaining of isolated alveolar type 2 cells. In the proximal airways, TIM was colocalized with CCSP to nonciliated columnar epithelial cells. Antisense oligonucleotides to mTim specifically inhibited branching morphogenesis of embryonic lungs in explant culture without affecting SpC expression an alveolar type 2 cell marker. In cultured lung cells, expression of TIM is independent of cell cycle and proliferation. These studies indicate that the function of Timeless is highly conserved in organs whose formation requires branching morphogenesis. Developmental Dynamics 228:82,94, 2003. © 2003 Wiley-Liss, Inc. [source]

T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung

DEVELOPMENTAL DYNAMICS, Issue 1 2003
Judith A. Cebra-Thomas
Abstract The regulation of signaling pathways is a prerequisite for coordinating the induction between mesenchymal and epithelial tissues during morphogenesis. Mesenchymal FGF10 is known to be an important paracrine factor regulating the branching morphogenesis of the bronchial epithelium. By using antisense oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the expression of mesenchymal FGF10. Treatment of embryonic lung cultures with AS ODNs to Tbx4 and Tbx5 reduces the level of these transcripts, suppresses Fgf10 expression in the mesenchyme, and completely eliminates the formation of new lung branches. If FGF10 is locally replaced in these AS ODN-treated lungs, epithelial branching is restored. These studies provide evidence that the production of branching signals by the lung mesenchyme is mediated by T-box genes. © 2002 Wiley-Liss, Inc. [source]

Inorganic arsenic as a developmental toxicant: In utero exposure and alterations in the developing rat lungs

MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2009
Jay S. Petrick
Abstract In the present study, we characterize the toxic effects of in utero arsenic exposure on the developing lung. We hypothesize that in utero exposure to inorganic arsenic through maternal drinking water causes altered gene and protein expression in the developing lung, indicative of downstream molecular and functional changes. From conception to embryonic day 18, we exposed pregnant Sprague-Dawley rats to 500 ppb arsenic (as arsenite) via the drinking water. Subtracted cDNA libraries comparing control to arsenic exposed embryonic lungs were generated. In addition, a broad Western blot analysis was performed to identify altered protein expression. A total of 59 genes and 34 proteins were identified as being altered. Pathway mapping and analysis showed that cell motility was the process most affected. The most likely affected pathway was alteration in integrin signaling through the ,-catenin pathway, altering c-myc. The present study shows that arsenic induces alterations in the developing lung. These data may be useful in the elucidation of molecular targets and biomarkers of arsenic exposure during lung development and may aid in understanding the etiology of arsenic induced adult respiratory disease and lung cancers. [source]