Decreased expression of transporters reduces folate uptake across renal absorptive surfaces in experimental alcoholism.
In this study, we examined the mechanistic insights of folate reabsorption during alcoholism, considering enhanced renal excretion as one of the major contributing factors to alcohol-induced folate deficiency. Male Wistar rats were fed 1g/kg body weight/day ethanol (20% solution) orally for 3 months. The results on characterization of the folate transport system in renal basolateral membrane (BLM) suggested it to be a carrier-mediated, acidic pH-dependent and saturable one. Chronic ethanol feeding decreased the uptake mainly by increasing the K (m) and decreasing the V (max) of the transport process at the BLM surface. At the molecular level, reduced folate transport activity in renal tissue during chronic ethanol ingestion was attributable to decreased expression of reduced folate carrier (RFC) and folate binding protein (FBP). Antibodies against RFC protein revealed a parallel change in RFC expression in both brush border and BLM surfaces during chronic alcoholism. Such findings highlight the role of downregulation of RFC and FBP expression and provide mechanistic insight into the observed reduced folate transport efficiency at renal absorptive surfaces in alcoholism, which may result in low blood folate levels commonly observed in alcoholics.
Hamid
Abid
A
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
Kaur
Jyotdeep
J
D000437:Alcoholism / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism / Q000493:pharmacokinetics*; D005494:Folic Acid Deficiency / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058978:Reduced Folate Carrier Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D026901:Membrane Transport Proteins; D011956:Receptors, Cell Surface; D058978:Reduced Folate Carrier Protein; D000431:Ethanol; D005492:Folic Acid