ИСТИНА

Methanol (MeOH) is considered to be a poison in humans because of the alcohol dehydrogenase (ADH)-mediated conversion of MeOH into toxic formaldehyde (FA) (1). 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 the modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels (2). 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. Experiments with volunteers after ethanol intake as an ADH “inhibitor” can assess lower-level MeOH production by endogenous sources. Ignoring the low contribution of renal and pulmonary clearance, we estimated the approximate lower level of endogenous MeOH production is at least ≈1.66 mg/kg/h. A microarray analysis of white blood cells (WBC) in volunteers after pectin intake showed various responses for 30 differentially regulated mRNAs. Most of the mRNAs 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 did not show significant change. A qRT-PCR analysis of volunteer WBC after pectin and red wine intake confirmed the complicated dependence between plasma MeOH content and the mRNA accumulation of previously identified genes, namely GAPDH and SNX27, and MME, SORL1, DDIT4, HBA and HBB genes revealed in this study. The identification of human genes, the transcriptional activity of which varies with the blood levels of MeOH, would lie between three possible functions of MeOH in humans as follows: (a) MeOH, a poisonous waste product, (b) MeOH, a signaling molecule that regulates the life processes, and (c) MeOH, a Janus-like substance similar to carbon dioxide that is released from the body during respiration, but without which the brain respiration centers cannot be activated. Our microarray analysis allows us to cede to the third hypothesis, which includes not only the inevitable involvement of MeOH-to-FA toxic metabolite formation but also the participation of MeOH in the regulation of gene involved in AD pathogenesis and signaling. References 1. Dorokhov Y.L., et al. (2012). Methanol may function as a cross-kingdom signal. PLoS One 7(4):e36122. 2. Komarova T.V., et al. (2014). Endogenous methanol regulates mammalian gene activity. PLoS One 9(2): e90239.