Differential expression of proteins in fetal brains of alcohol-treated prenatally C57BL/6 mice: a proteomic investigation.
Alcohol is known to impede the growth of the central nervous system and to induce neurodegeneration through cellular apoptosis. We have previously shown that moderate prenatal alcohol exposure results in brain defects at different stages of development. In this study, we further characterize the proteomic architecture underlying ethanol teratogenesis during early fetal brain development using chromatography in conjunction with a LC-MS/MS system. Pregnant C57BL/6 mice were exposed from embryonic day 7 (E7) to E13 with either a 25% ethanol derived calorie or pair-fed liquid diets. At E13, fetal brains were collected from five dams for each group. Individual brains were homogenized and the extracted proteins were then tryptically digested and analyzed by LC-MS/MS. Label-free quantitative proteomic analyses were performed on proteomes extracted from fetal brains of both alcohol-treated (ALC) and pair-fed groups. These analyses demonstrated that prenatal alcohol exposure induced significant downregulation (p<0.001) of the expression of mitochondrial enzymes including ADP/ATP translocase 1, ATP synthase subunit alpha and ubiquinol-cytochrome-c reductases. In addition, mitochondrial carrier homolog 1, which plays a role in apoptosis, was significantly downregulated (p<0.001) in the ALC group. Moreover, among the cytosolic proteins that were significantly downregulated (p<0.001) are Bcl-2, 14-3-3 protein and calmodulin. Significant downregulation (p<0.001) of proteins that are critical for fetal brain development was observed such as prohibitin and neuronal migration protein doublecortin. These findings provide information about possible mechanisms underlying the effects of prenatal alcohol exposure during early embryonic stage.
Sari
Youssef
Y
Neuroscience Program, Department of Psychological and Brain Sciences, Indiana University Bloomington, IN 47405, USA. ysari@indiana.edu
Zhang
Min
M
Mechref
Yehia
Y
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D002853:Chromatography, Liquid; D003600:Cytosol / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D013058:Mass Spectrometry; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D013723:Teratogens / Q000633:toxicity
D011506:Proteins; D013723:Teratogens; D000431:Ethanol