Biochemical and Molecular Mechanisms of Folate Transport in Rat Pancreas; Interference with Ethanol Ingestion

Nissar Ahmad Wani,Ritambhara Nada,Jyotdeep Kaur,Julio Francisco Turrens

doi:10.1371/journal.pone.0028599

Nissar Ahmad Wani, Ritambhara Nada + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0028599

Copy DOI

Abstract

Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency which is due, in part to folate malabsorption. The present study deals with the mechanistic insights of reduced folate absorption in pancreas during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and the mechanisms of alcohol associated reduced folate uptake was studied in pancreas. The folate transport system in the pancreatic plasma membrane (PPM) was found to be acidic pH dependent one. The transporters proton coupled folate transporter (PCFT) and reduced folate carrier (RFC) are involved in folate uptake across PPM. The folate transporters were found to be associated with lipid raft microdomain of the PPM. Ethanol ingestion decreased the folate transport by reducing the levels of folate transporter molecules in lipid rafts at the PPM. The decreased transport efficiency of the PPM was reflected as reduced folate levels in pancreas. The chronic ethanol ingestion led to decreased pancreatic folate uptake. The decreased levels of PCFT and RFC expression in rat PPM were due to decreased association of these proteins with lipid rafts (LR) at the PPM.

Highlights

Folate is a member of vitamin B group and is required for the transfer of one carbon unit during nucleic acid synthesis and for metabolism of amino acid [1,2]
The folate uptake studied at 10 seconds, the measurement time selected as a time point just prior to the uptake maxima observed in both the groups, revealed less folate uptake in ethanol fed rats as compared to control (Figure 1)
Despite the importance of folate for the exocrine pancreas, little is known about the regulation of folate transport across the pancreatic plasma membrane (PPM) and interference in uptake by ethanol consumption

Summary

Introduction

Folate is a member of vitamin B group and is required for the transfer of one carbon unit during nucleic acid synthesis and for metabolism of amino acid [1,2]. For this reason, cellular deficiency of this essential micronutrient in certain organs leads to disturbances in the normal physiology of the cell that is manifested in the form of undesirable clinical symptoms. Studying the molecular mechanisms regulating the folate uptake by the pancreatic cells is of physiological, nutritional, and clinical importance

Methods

Results

Conclusion