Developmental cigarette smoke exposure II: Hepatic proteome profiles in 6 month old adult offspring.

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.

Soy glyceollins regulate transcript abundance in the female mouse brain.

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown. For this study, we implanted 17-ß estradiol (E2) or placebo slow-release pellets into ovariectomized CFW mice followed by 11 days of exposure to Gly or vehicle i.p. injections. We then performed a microarray on total RNA extracted from whole-brain hemispheres and identified differentially expressed genes (DEGs) by a 2 × 2 factorial ANOVA with an false discovery rate (FDR) = 0.20. In total, we identified 33 DEGs with a significant E2 main effect, 5 DEGs with a significant Gly main effect, 74 DEGs with significant Gly and E2 main effects (but no significant interaction term), and 167 DEGs with significant interaction terms. Clustering across all DEGs revealed that transcript abundances were similar between the E2 + Gly and E2-only treatments. However, gene expression after Gly-only treatment was distinct from both of these treatments and was generally characterized by higher transcript abundance. Collectively, our results suggest that whether Gly acts in the brain through ER-dependent or ER-independent mechanisms depends on the target gene.

Prenatal alcohol exposure alters the cerebral cortex proteome in weanling rats.

Maternal consumption of alcohol during pregnancy impairs neurodevelopment in offspring. Utilizing a rodent model of continuous moderate dose alcohol exposure throughout gestation [gestation day 1 (GD1)-GD22; BAC ~70 mg/dL], the impact of developmental alcohol exposure on juvenile cerebral cortex protein abundances was determined. At weaning, cerebral cortex tissue was collected from pups for 2D SDS-PAGE based proteome analysis with statistical analysis by Partial Least Squares-Discriminant Analysis (PLS-DA). Gestational alcohol exposure increased the abundance of post-translationally modified forms of cytoskeletal proteins and the abundance of proteins within the small molecule biochemistry (includes glucose metabolism) pathway and proteosome processing pathways though ubiquitin conjugating enzymes and chaperones were decreased in abundance. In weanling offspring exposed prenatally to alcohol, alterations in cytoskeletal protein post-translational modifications were noted. Increased abundance of proteins from the small molecule biochemistry pathway, which includes glucose metabolism, and proteosome processing pathways were also noted. Decreased abundances of ubiquitin conjugating enzyme and chaperone protein were noted in the cerebral cortex of these offspring.