PMID- 21478255
OWN - NLM
STAT- MEDLINE
DCOM- 20110831
LR  - 20231213
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 301
IP  - 1
DP  - 2011 Jul
TI  - Thirdhand smoke: a new dimension to the effects of cigarette smoke on the 
      developing lung.
PG  - L1-8
LID - 10.1152/ajplung.00393.2010 [doi]
AB  - 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 a 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. 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 24 h. We then determined 
      key markers for alveolar paracrine signaling [epithelial differentiation markers 
      surfactant phospholipid and protein synthesis; mesenchymal differentiation 
      markers peroxisome proliferator-activated receptor gamma (PPAR-gamma), fibronectin and 
      calponin], the BCL-2-to-Bax ratio (BCL-2/Bax), a marker of apoptosis and the 
      involvement of nicotinic acetylcholine receptors (nAChR)-alpha3 and -alpha7 in mediating 
      NNA's and NNK's effects on the developing lung. Similar to the effects of 
      nicotine, exposure of the developing lung to either NNK or NNA resulted in 
      disrupted homeostatic signaling, indicated by the downregulation of PPAR-gamma, 
      upregulation of fibronectin and calponin protein levels, decreased BCL-2/Bax, and 
      the accompanying compensatory stimulation of surfactant phospholipid and protein 
      synthesis. Furthermore, nAChR-alpha3 and -alpha7 had differential complex roles in 
      mediating these effects. 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.
FAU - Rehan, Virender K
AU  - Rehan VK
AD  - Departments of Pediatrics, Los Angeles Biomedical Research Institute at 
      Harbor-UCLA Medical Center, Torrance, California 90502, USA. vrehan@labiomed.org
FAU - Sakurai, Reiko
AU  - Sakurai R
FAU - Torday, John S
AU  - Torday JS
LA  - eng
GR  - HD51857/HD/NICHD NIH HHS/United States
GR  - HD058948/HD/NICHD NIH HHS/United States
GR  - R01 HD051857/HD/NICHD NIH HHS/United States
GR  - HL75405/HL/NHLBI NIH HHS/United States
GR  - R01 HD051857-03/HD/NICHD NIH HHS/United States
GR  - HL55268/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110408
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Aldehydes)
RN  - 0 (Bungarotoxins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Nitrosamines)
RN  - 0 (PPAR gamma)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (Tobacco Smoke Pollution)
RN  - 6EE945D3OK (Mecamylamine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 7S395EDO61 (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone)
RN  - H21352682A (butyraldehyde)
SB  - IM
MH  - Aldehydes/toxicity
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Bungarotoxins/pharmacology
MH  - Calcium-Binding Proteins/metabolism
MH  - Lung/*drug effects/*embryology/pathology
MH  - Mecamylamine/pharmacology
MH  - Microfilament Proteins/metabolism
MH  - Nicotine/toxicity
MH  - Nitrosamines/toxicity
MH  - PPAR gamma/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Nicotinic/metabolism
MH  - Smoking/*adverse effects
MH  - Tobacco Smoke Pollution/*adverse effects
MH  - Calponins
PMC - PMC3129897
EDAT- 2011/04/12 06:00
MHDA- 2011/09/01 06:00
PMCR- 2012/07/01
CRDT- 2011/04/12 06:00
PHST- 2011/04/12 06:00 [entrez]
PHST- 2011/04/12 06:00 [pubmed]
PHST- 2011/09/01 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - ajplung.00393.2010 [pii]
AID - L-00393-2010 [pii]
AID - 10.1152/ajplung.00393.2010 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2011 Jul;301(1):L1-8. doi: 
      10.1152/ajplung.00393.2010. Epub 2011 Apr 8.