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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.

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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.

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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.