PMID- 22609517 OWN - NLM STAT- MEDLINE DCOM- 20120921 LR - 20240318 IS - 1879-3185 (Electronic) IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 300 IP - 1-2 DP - 2012 Oct 9 TI - Developmental cigarette smoke exposure: liver proteome profile alterations in low birth weight pups. PG - 1-11 LID - 10.1016/j.tox.2012.04.016 [doi] AB - Cigarette smoke is composed of over 4000 chemicals many of which are strong oxidizing agents and chemical carcinogens. Chronic cigarette smoke exposure (CSE) induces mild alterations in liver histology indicative of toxicity though the molecular pathways underlying these alterations remain to be explored. Utilizing a mouse model of 'active' developmental CSE (gestational day (GD) 1 through postnatal day (PD) 21; cotinine >50ng/mL) characterized by low birth weight offspring, the impact of developmental CSE on liver protein abundances was determined. On PD21, liver tissue was collected from pups for 2D SDS-PAGE based proteome analysis with statistical analysis by Partial Least Squares-Discriminant Analysis (PLS-DA). Protein spots of interest were identified by ESI-MS/MS with impacted molecular pathways identified by Ingenuity Pathway Analysis. Developmental CSE decreased the abundance of proteins associated with the small molecule biochemistry (includes glucose metabolism), lipid metabolism, amino acid metabolism, and inflammatory response pathways. Decreased gluconeogenic enzyme activity and lysophosphatidylcholine availability following developmental CSE were found and supports the impact of CSE on these pathways. Proteins with increased abundance belonged to the cell death and drug metabolism networks. Liver antioxidant enzyme abundances [glutathione-S-transferase (GST) and peroxiredoxins] were also altered by CSE, but GST enzymatic activity was unchanged. In summary, cigarette smoke exposure spanning pre- and post-natal development resulted in persistent decreased offspring weights, decreased abundances of liver metabolic proteins, decreased gluconeogenic activity, and altered lipid metabolism. The companion paper details the kidney proteome alterations in the same offspring. CI - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved. FAU - Canales, Lorena AU - Canales L AD - Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, USA. FAU - Chen, Jing AU - Chen J FAU - Kelty, Elizabeth AU - Kelty E FAU - Musah, Sadiatu AU - Musah S FAU - Webb, Cindy AU - Webb C FAU - Pisano, M Michele AU - Pisano MM FAU - Neal, Rachel E AU - Neal RE LA - eng GR - P30 ES014443/ES/NIEHS NIH HHS/United States GR - P20 GM103453/GM/NIGMS NIH HHS/United States GR - R21 DA027466/DA/NIDA NIH HHS/United States GR - P20 RR017702/RR/NCRR NIH HHS/United States GR - P20 RR/DE-17702/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20120515 PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Proteome) RN - 0 (Tobacco Smoke Pollution) SB - IM MH - Animals MH - Animals, Newborn/blood/growth & development MH - Disease Models, Animal MH - Electrophoresis, Gel, Two-Dimensional MH - Female MH - Gluconeogenesis/drug effects MH - Inhalation Exposure/adverse effects MH - Liver/chemistry/*drug effects/enzymology MH - Male MH - Mass Spectrometry MH - Metabolome/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Proteome/*analysis MH - Tobacco Smoke Pollution/*adverse effects PMC - PMC3699338 MID - NIHMS378672 EDAT- 2012/05/23 06:00 MHDA- 2012/09/22 06:00 PMCR- 2013/10/09 CRDT- 2012/05/22 06:00 PHST- 2010/11/01 00:00 [received] PHST- 2012/04/23 00:00 [revised] PHST- 2012/04/25 00:00 [accepted] PHST- 2012/05/22 06:00 [entrez] PHST- 2012/05/23 06:00 [pubmed] PHST- 2012/09/22 06:00 [medline] PHST- 2013/10/09 00:00 [pmc-release] AID - S0300-483X(12)00163-1 [pii] AID - 10.1016/j.tox.2012.04.016 [doi] PST - ppublish SO - Toxicology. 2012 Oct 9;300(1-2):1-11. doi: 10.1016/j.tox.2012.04.016. Epub 2012 May 15.