Neal Rachel E, Chen Jing, Webb Cindy, Stocke Kendall, Gambrell Caitlin, Greene Robert M, Pisano M Michele
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States; Birth Defects Center, University of Louisville, Louisville, KY, United States.
Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY, United States.
Reprod Toxicol. 2016 Oct;65:414-424. doi: 10.1016/j.reprotox.2016.06.009. Epub 2016 Jun 16.
Utilizing a mouse model of 'active' developmental cigarette smoke exposure (CSE) [gestational day (GD) 1 through postnatal day (PD) 21] characterized by offspring low birth weight, the impact of developmental CSE on liver proteome profiles of adult offspring at 6 months of age was determined. Liver tissue was collected from Sham- and CSE-offspring for 2D-SDS-PAGE based proteome analysis with Partial Least Squares-Discriminant Analysis (PLS-DA). A similar study conducted at the cessation of exposure to cigarette smoke documented decreased gluconeogenesis coupled to oxidative stress in weanling offspring. In the current study, exposure throughout development to cigarette smoke resulted in impaired hepatic carbohydrate metabolism, decreased serum glucose levels, and increased gluconeogenic regulatory enzyme abundances during the fed-state coupled to decreased expression of SIRT1 as well as increased PEPCK and PGC1α expression. Together these findings indicate inappropriately timed gluconeogenesis that may reflect impaired insulin signaling in mature offspring exposed to 'active' developmental CSE.
利用一种以子代低出生体重为特征的“主动”发育性香烟烟雾暴露（CSE）小鼠模型（孕期第1天至出生后第21天），确定了发育性CSE对6月龄成年子代肝脏蛋白质组图谱的影响。从假暴露组和CSE组子代收集肝脏组织，用于基于二维十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（2D-SDS-PAGE）的蛋白质组分析，并进行偏最小二乘判别分析（PLS-DA）。一项在停止香烟烟雾暴露时进行的类似研究记录了断奶子代中糖异生减少与氧化应激相关。在当前研究中，整个发育过程中暴露于香烟烟雾导致肝脏碳水化合物代谢受损、血清葡萄糖水平降低，在进食状态下糖异生调节酶丰度增加，同时SIRT1表达降低以及磷酸烯醇式丙酮酸羧激酶（PEPCK）和过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）表达增加。这些发现共同表明糖异生时机不当，这可能反映了暴露于“主动”发育性CSE的成熟子代中胰岛素信号传导受损。
