High-throughput caveolar proteomic signature profile for maternal binge alcohol consumption - PubMed (original) (raw)

High-throughput caveolar proteomic signature profile for maternal binge alcohol consumption

Jayanth Ramadoss et al. Alcohol. 2010 Nov-Dec.

Abstract

Currently, no single marker is sensitive and specific enough to be considered a reliable biomarker for prenatal alcohol exposure. To identify a proteomic signature profile for maternal alcohol consumption, we carried out high-throughput proteomics on maternal endothelial caveolae exposed to moderate binge-like alcohol conditions. In these specialized lipid-ordered microdomains that contain a rich assembly of proteins, we demonstrate that moderate binge-like alcohol resulted in a distinctive maternal caveolar proteomic signature with important proteins being dramatically decreased/knocked out in the alcoholic profile. These proteins span from histones and basic structural proteins like α tubulin to proteins involved in trafficking, deubiquitination, cell signaling, and cell-cell adhesion. The profile also suggests an important role for the mother and the uteroplacental compartment in the pathogenesis of fetal alcohol spectrum disorders (FASD). These data demonstrate that the caveolar proteomic signature created by alcohol shows a promising direction for early detection of FASD.

Copyright © 2010 Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1

(A) Representative MS/MS spectra of cav-1 and eNOS illustrate a nearly complete Y ion series assignment. The B ion series confirm peptide assignment. All major signals in the spectra are explained by the assigned sequences. Sequest cross correlation scores for cav-1 and eNOS are 4.58 and 4.08 respectively. Cav-1 and eNOS parent mass error are −0.39 PPM and −1.8 PPM respectively. (B) Chronic binge-like alcohol exposure resulted in dramatic decreases in the abundance of endothelial caveolar proteins related to cell-cell adhesion, cell function, cell signaling, deubiquitination, histones, nitric oxide/vascular tone, structure, and transport/trafficking. Pie chart slices bound by solid lines represent the caveolar protein abundance in control state. The shaded subset in each slice represents the caveolar protein abundance in response to chronic binge alcohol.

Figure 2

Figure 2

Chronic binge-like alcohol exposure resulted in a distinctive endothelial caveolar proteomic signature profile that included proteins related to cell-cell adhesion, cell function, cell signaling, deubiquitination, histones, nitric oxide/vascular tone, structure, and transport/trafficking. Profile details and abbreviations are described in the Results section. The caveolar protein profile is depicted as % of control.

Figure 3

Figure 3

Western immunoblot analysis of gradient density centrifugation of subcellular fractions fractions prepared from (A) control (0 mg/dl) and (B) binge alcohol (150 mg/dl) treated uterine arterial endothelial cells from pregnant ewes. Under control conditions, cav-1 and eNOS were both predominantly located in the caveolar pool (lanes 4–5; figure 2A) whereas endothelial nitric oxide synthase was entirely depleted from this caveolar pool in response to binge-like alcohol (figure 2B).

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