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Published on: May 6, 2022
Dietary methanol regulates human gene activity
Anastasia V Shindyapina1, Igor V Petrunia2, Tatiana V Komarova1
1A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia; N. I. Vavilov Institute of General Genetics, Russian Academy of Science, Moscow, Russia.
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.
Insights
Consuming citrus pectin, ethanol, or red wine increased methanol and formaldehyde in blood plasma. This suggests methanol impacts white blood cell mRNA levels, potentially influencing cell signaling and Alzheimer's disease pathogenesis.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- Methanol (MeOH) is toxic due to its conversion to formaldehyde (FA) by alcohol dehydrogenase (ADH).
- Previous mouse studies indicated endogenous MeOH influences homeostasis by regulating mRNA synthesis.
- The role of MeOH in human physiological responses requires further investigation.
Purpose of the Study:
- To investigate the impact of consuming common substances on plasma methanol and formaldehyde levels in humans.
- To analyze changes in white blood cell (WBC) mRNA profiles following pectin intake.
- To explore the relationship between plasma MeOH and mRNA expression in human WBCs.
Main Methods:
- Blood plasma analysis for methanol and formaldehyde concentrations.
- Microarray analysis of WBCs to identify differentially regulated mRNAs.
- Quantitative reverse transcription PCR (qRT-PCR) to validate mRNA expression levels.
Main Results:
- Citrus pectin, ethanol, and red wine consumption led to increased plasma MeOH and FA concentrations.
- Pectin intake altered mRNA synthesis in WBCs, with several genes linked to Alzheimer's disease pathogenesis showing differential regulation.
- Decreased synthesis of hemoglobin mRNA (HBA and HBB) was observed in WBCs, independent of red blood cell contamination.
- Plasma MeOH levels showed a complex correlation with mRNA accumulation of specific genes (GAPDH, SNX27, MME, SORL1, DDIT4, HBA, HBB).
Conclusions:
- Human consumption of pectin, ethanol, and red wine can elevate plasma methanol and formaldehyde.
- Plasma methanol may influence mRNA levels in human white blood cells, particularly genes involved in cell signaling.
- These findings suggest a potential role for methanol in pathways relevant to Alzheimer's disease and other conditions.
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