| Thirdhand Smoke: A New Dimension to the Effects of Cigarette Smoke on the Developing Lung. | |
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MedLine Citation:
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PMID: 21478255 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rationale: The underlying mechanisms and effector molecules involved in mediating in utero smoke exposure-induced effects on the developing lung are only beginning to be understood. However, the effects of the newly discovered category of smoke, i.e., thirdhand smoke (THS), on the developing lung are completely unknown. We hypothesized that in addition to nicotine, other components of THS would also affect lung development adversely. Methods: Fetal rat lung explants were exposed to nicotine, 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the two main tobacco-specific N-nitrosamine constituents of THS, for 24h. Following which key markers for alveolar paracrine signaling [epithelial differentiation markers, surfactant phospholipid and protein synthesis and mesenchymal differentiation markers, PPARγ, fibronectin, and calponin], the BCL-2/Bax ratio, a marker of apoptosis, and the involvement of nicotinic acetylcholine receptors (nAChR)-α3 and -α7 in mediating NNA's and NNK's effects on the developing lung were determined. Main Results: Similar to the effects of nicotine, exposure of the developing lung to either NNK or NNA resulted in disrupted homeostatic signaling, indicated by the down-regulation of PPARγ, up-regulation of fibronectin and calponin protein levels, decreased BCL-2/Bax ratio, and the accompanying compensatory stimulation of surfactant phospholipid and protein synthesis. Furthermore, nAChR-α3 and -α7 had differential complex roles in mediating these effects. Conclusions: NNK and NNA exposure resulted in breakdown of alveolar epithelial-mesenchymal cross-talk, reflecting lipofibroblast-to-myofibroblast transdifferentiation, suggesting THS constituents as possible novel contributors to in utero smoke exposure-induced pulmonary damage. These data are particularly relevant for designing specific therapeutic strategies, and for formulating public health policies to minimize THS exposure. |
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Authors:
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Virender K Rehan; Reiko Sakurai; John S Torday |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-8 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Harbor UCLA Medical Center. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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