2.50
Hdl Handle:
http://hdl.handle.net/10755/211632
Type:
Research Study
Title:
CIGARETTE SMOKE EXTRACT-INDUCED CHANGES IN TELOMERES OF LUNG ALVEOLAR CELLS
Abstract:
Background: Cigarette smoke (CS) is the single greatest factor in the development of chronic obstructive pulmonary disease (COPD). CS may affect telomeres, structures at the ends of chromosomes that shorten with each cell division, by accelerating telomere shortening which critically impacts cell function and cell division and ultimately leads to disease—i.e. COPD. The actions of second and third hand smoke, which have implications for the future pulmonary health of non-smokers and the very young, are just beginning to be appreciated.  It is known that CS affects the cells of the alveolus, or gas exchanging unit of the lung; the alveolus is composed of alveolar epithelial type I (AT I) cells and microvascular endothelial cells (MVECs). However, the effects of CS on telomeres of AT I cells and MVECs are unknown. Purpose: The purpose of this study was to determine the effect of cigarette smoke extract (CSE) exposure on relative telomere length of AT I cells and MVECs. Methods: CSE preparations were standardized using research grade cigarettes. AT I cells and MVECs were harvested from the lungs of neonatal (7 day), young (3 months) and old (24 months) male Fischer 344 rats. Each age group of AT I cells and MVECs were cultured separately and then exposed to 2% CSE for 3 weeks. Relative telomere length was determined using RT qPCR. Gene expression profiling specific to telomere maintenance and telomerase pathways was used to assess for potential molecular mechanisms involved in CSE-induced changes in telomere length. Results: CSE exposure shortened telomeres of neonatal AT I cells (p<0.05) while CSE exposed young and old AT I cells demonstrated longer telomeres than controls (p<0.05). CSE exposure resulted in shorter telomeres in neonatal MVECs (p<0.05) but did not affect telomere length in young and old MVECs. Gene expression profiling identified 6 genes in neonates and 7 genes in old AT I cells that were affected by CSE exposure. Comparison of gene expression between neonatal and old AT I cells exposed to CSE revealed that CSE exposure stimulated cell division in neonates and promoted growth arrest in old AT I cells. Discussion: CSE affects neonatal cells differently than young and old cells. CSE exposure accelerated telomere shortening in neonatal AT I cells and MVECs, an observation that both furthers our understanding of how CS affects the lung and has implications for the future pulmonary health of neonates exposed to second and/or third hand smoke.
Keywords:
Cigarette smoke; Telomeres; Chronic obstructive pulmonary disease
Repository Posting Date:
20-Feb-2012
Date of Publication:
20-Feb-2012
Other Identifiers:
5594
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typeResearch Studyen_GB
dc.titleCIGARETTE SMOKE EXTRACT-INDUCED CHANGES IN TELOMERES OF LUNG ALVEOLAR CELLSen_GB
dc.identifier.urihttp://hdl.handle.net/10755/211632-
dc.description.abstractBackground: Cigarette smoke (CS) is the single greatest factor in the development of chronic obstructive pulmonary disease (COPD). CS may affect telomeres, structures at the ends of chromosomes that shorten with each cell division, by accelerating telomere shortening which critically impacts cell function and cell division and ultimately leads to disease—i.e. COPD. The actions of second and third hand smoke, which have implications for the future pulmonary health of non-smokers and the very young, are just beginning to be appreciated.  It is known that CS affects the cells of the alveolus, or gas exchanging unit of the lung; the alveolus is composed of alveolar epithelial type I (AT I) cells and microvascular endothelial cells (MVECs). However, the effects of CS on telomeres of AT I cells and MVECs are unknown. Purpose: The purpose of this study was to determine the effect of cigarette smoke extract (CSE) exposure on relative telomere length of AT I cells and MVECs. Methods: CSE preparations were standardized using research grade cigarettes. AT I cells and MVECs were harvested from the lungs of neonatal (7 day), young (3 months) and old (24 months) male Fischer 344 rats. Each age group of AT I cells and MVECs were cultured separately and then exposed to 2% CSE for 3 weeks. Relative telomere length was determined using RT qPCR. Gene expression profiling specific to telomere maintenance and telomerase pathways was used to assess for potential molecular mechanisms involved in CSE-induced changes in telomere length. Results: CSE exposure shortened telomeres of neonatal AT I cells (p<0.05) while CSE exposed young and old AT I cells demonstrated longer telomeres than controls (p<0.05). CSE exposure resulted in shorter telomeres in neonatal MVECs (p<0.05) but did not affect telomere length in young and old MVECs. Gene expression profiling identified 6 genes in neonates and 7 genes in old AT I cells that were affected by CSE exposure. Comparison of gene expression between neonatal and old AT I cells exposed to CSE revealed that CSE exposure stimulated cell division in neonates and promoted growth arrest in old AT I cells. Discussion: CSE affects neonatal cells differently than young and old cells. CSE exposure accelerated telomere shortening in neonatal AT I cells and MVECs, an observation that both furthers our understanding of how CS affects the lung and has implications for the future pulmonary health of neonates exposed to second and/or third hand smoke.en_GB
dc.subjectCigarette smokeen_GB
dc.subjectTelomeresen_GB
dc.subjectChronic obstructive pulmonary diseaseen_GB
dc.date.available2012-02-20T12:05:15Z-
dc.date.issued2012-02-20T12:05:15Z-
dc.date.accessioned2012-02-20T12:05:15Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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