Dietary methanol regulates human gene activity.

Anastasia V Shindyapina,Vyacheslav S Kosorukov,Yuri L Dorokhov,Ekaterina V Sheshukova,Gleb I Kiryanov,Igor V Petrunia,Tatiana V Komarova,Klaus Roemer

doi:10.1371/journal.pone.0102837

Anastasia V Shindyapina, Vyacheslav S Kosorukov + Show 6 more

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https://doi.org/10.1371/journal.pone.0102837

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Abstract

Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH to formaldehyde (FA), which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC) from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD). There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

Highlights

Robert Boyle first described wood spirits, or methanol (MeOH), as the ‘‘sowrish spirit’’ of boxwood pyrolysis in 1661 [1], and its function in plant and animal life has since been unclear
The effects of pectin methylesterase (PME)-generated MeOH from plants-emitters on plants-receivers’ were recently studied [2]. These investigations demonstrated that increased MeOH emissions from PME-transgenic or mechanically wounded non-transgenic plants retard the growth of bacterial pathogen Ralstonia solanacearum in neighboring ‘‘receiver’’ plants
To test the role of alcohol dehydrogenase (ADH) in maintaining a low MeOH concentration, we recently showed that the intraperitoneal administration of 4-MP resulted in a significant increase MeOH, EtOH and FA concentrations in mouse plasma [47]

Summary

Introduction

Robert Boyle first described wood spirits, or methanol (MeOH), as the ‘‘sowrish spirit’’ of boxwood pyrolysis in 1661 [1], and its function in plant and animal life has since been unclear. The effects of PME-generated MeOH from plants-emitters on plants-receivers’ were recently studied [2]. These investigations demonstrated that increased MeOH emissions from PME-transgenic or mechanically wounded non-transgenic plants retard the growth of bacterial pathogen Ralstonia solanacearum in neighboring ‘‘receiver’’ plants. This antibacterial resistance is accompanied by the up-regulation of genes that control stress and cell-to-cell communication in the ‘‘receiver’’. These results suggest that MeOH is a signaling molecule for within-plant and plant-to-plant communications [2]

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