Cruciferous vegetable supplementation in a controlled diet study alters the serum peptidome in a GSTM1-genotype dependent manner

Abstract

BackgroundCruciferous vegetable intake is inversely associated with the risk of several cancers. Isothiocyanates (ITC) are hypothesized to be the major bioactive constituents contributing to these cancer-preventive effects. The polymorphic glutathione-S-transferase (GST) gene family encodes several enzymes which catalyze ITC degradation in vivo.MethodsWe utilized high throughput proteomics methods to examine how human serum peptides (the "peptidome") change in response to cruciferous vegetable feeding in individuals of different GSTM1 genotypes. In two randomized, crossover, controlled feeding studies (EAT and 2EAT) participants consumed a fruit- and vegetable-free basal diet and the basal diet supplemented with cruciferous vegetables. Serum samples collected at the end of the feeding period were fractionated and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry spectra were obtained. Peak identification/alignment computer algorithms and mixed effects models were used to analyze the data.ResultsAfter analysis of spectra from EAT participants, 24 distinct peaks showed statistically significant differences associated with cruciferous vegetable intake. Twenty of these peaks were driven by their GSTM1 genotype (i.e., GSTM1+ or GSTM1- null). When data from EAT and 2EAT participants were compared by joint processing of spectra to align a common set, 6 peaks showed consistent changes in both studies in a genotype-dependent manner. The peaks at 6700 m/z and 9565 m/z were identified as an isoform of transthyretin (TTR) and a fragment of zinc α2-glycoprotein (ZAG), respectively.ConclusionsCruciferous vegetable intake in GSTM1+ individuals led to changes in circulating levels of several peptides/proteins, including TTR and a fragment of ZAG. TTR is a known marker of nutritional status and ZAG is an adipokine that plays a role in lipid mobilization. The results of this study present evidence that the GSTM1-genotype modulates the physiological response to cruciferous vegetable intake.

The potential role of nutritional genomics tools in validating high health foods for cancer control: Broccoli as example

“…Several examples of such genetic stratification are summraised in Table 1 [86][87][88][89][90]. A good example is provided by a recent proteomic trial, where interpretation of the protein patterns found was possible only when the results were stratified according to glutathione S-transferase mu 1 (GSTM1) genotypes [86].…”

“…Several examples of such genetic stratification are summraised in Table 1 [86][87][88][89][90]. A good example is provided by a recent proteomic trial, where interpretation of the protein patterns found was possible only when the results were stratified according to glutathione S-transferase mu 1 (GSTM1) genotypes [86]. Steck and Hebert [107] summarised the literature showing an association between genotypic variation, measured as single nucleotide polymorphisms (SNPs), in glutathione S-transferase (GST) genes, and excretion of both dietary carcinogens and ITC metabolites after brassicaceous vegetable consumption.…”

Dermcidin expression is associated with disease progression and survival among breast cancer patients

“…An equal volume of 100 % acetonitrile was added to each serum sample to precipitate out large globular proteins as previously described [9, 10]. Samples were shaken for 30 min.…”

“…Previously, we developed analytical methods using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI–TOF MS) to identify changes in the serum peptidome [9, 10]. This type of spectrometry-based protein profiling has been used to identify novel diagnostic markers for disease [11, 15].…”

Plant Science and Human Nutrition: Challenges in Assessing Health-Promoting Properties of Phytochemicals

“…Foods rich in b-carotene have been used in several studies to investigate how they could be used to alleviate vitamin A deficiency (van Jaarsveld et al, 2005;Low et al, 2007) and other carotenoids, such as lycopene, lutein, and zeaxanthin, to investigate effects on biomarkers of cardiovascular risk, DNA damage, inflammation, and macular degeneration (Chopra et al, 2000;Astley et al, 2004;Kopsell et al, 2006;Paterson et al, 2006;Beck et al, 2010). There have also been several human intervention studies with cruciferous vegetables to attempt to obtain experimental evidence to support epidemiological data for the health promoting effects of these vegetables (Kensler et al, 2005;Al Janobi et al, 2006;Gasper et al, 2007;Traka et al, 2008;Li et al, 2009;Navarro et al, 2009aNavarro et al, , 2009bYanaka et al, 2009;Brauer et al, 2011). Systematic reviews of human intervention studies that have involved both carotenoid-rich and glucosinolaterich foods, as have been done for flavonoid-rich foods (Hooper et al, 2008), would be timely.…”