Proteomic Analysis of Baboon Cerebral Artery Reveals Potential Pathways of Damage by Prenatal Alcohol Exposure.

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ID: 47859
2019
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Abstract
Alcohol is one of the most widely misused substances in the world. Alcohol consumption by pregnant women often results in an array of fetal developmental abnormalities, but the damage to the fetus by alcohol remains poorly understood. The limited knowledge regarding the molecular targets of alcohol in the developing fetus constitutes one of the major obstacles in developing effective pharmacological interventions that could prevent fetal damage after alcohol consumption by pregnant women. The fetal cerebral artery is emerging as an important mediator of fetal cerebral damage by maternal alcohol drinking. In the present work, we conduct proteomics analysis of cerebral (basilar) artery lysates of near-term fetal baboons to search for protein targets of fetal alcohol exposure. Our study demonstrates that 3 episodes of binge alcohol exposure during the second trimester-equivalent of human pregnancy are sufficient to render profound changes in fetal cerebral artery proteome. These changes persisted, as they were detected in near-term fetuses. In particular, the relative abundance of 238 proteins differed significantly between control and alcohol-exposed fetuses. Enrichment analysis pointed at the group of metabolic activity proteins as a major class targeted by alcohol. Western blotting confirmed upregulation of the aldehyde dehydrogenase 6 family member A1 (ALDH6A1) in cerebral artery lysates from alcohol-exposed fetuses. This upregulation translated to greater ALDH activity of cerebral artery lysate of near-term fetuses following prenatal alcohol exposure when compared with controls.
Reference Key
bisen2019proteomicmolecular Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Bisen, Shivantika;Kakhniashvili, David;Johnson, Daniel L;Bukiya, Anna N;
Journal molecular & cellular proteomics : mcp
Year 2019
DOI
10.1074/mcp.RA118.001047
URL
Keywords
Mass spectrometry pregnancy physiology pharmacology networks animal models binge drinking alcohol in utero cardiovascular function or biology fetal alcohol syndrome and spectrum disorders maternal drinking mitochondria function or biology prenatal alcohol exposure

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