BACKGROUND: Folic acid [corrected] plays an essential role in cellular metabolism. Its deficiency can lead to neural tube defects. However, optimization of body folate homeostasis can reduce the incidence of neural tube defects and may decrease the risk of Alzheimer and cardiovascular diseases and cancer. Hence, food fortification and intake of supplemental folate are widespread. OBJECTIVE: We examined the effects of long-term folate oversupplementation on the physiologic markers of intestinal and renal folate uptake processes. DESIGN: Human-derived intestinal Caco-2 and renal HK-2 epithelial cells were maintained (5 generations) in a growth medium oversupplemented (100 micromol folic acid/L) or maintained under sufficient conditions (0.25 and 9 micromol folic acid/L). RESULTS: Carrier-mediated uptake of (3)H-folic acid (2 micromol/L) at buffer pH 5.5 (but not buffer pH 7.4) by Caco-2 and HK-2 cells maintained under the folate-oversupplemented condition was significantly (P<0.01) and specifically lower than in cells maintained under the folate-sufficient condition. This reduction in folic acid uptake was associated with a significant decrease in the protein and mRNA levels of the human reduced-folate carrier (hRFC) and a decrease in the activity of the hRFC promoter. It was also associated with a decrease in mRNA levels of the proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) and folate receptor (FR). CONCLUSIONS: Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.
BACKGROUND:Folic acid [corrected] plays an essential role in cellular metabolism. Its deficiency can lead to neural tube defects. However, optimization of body folate homeostasis can reduce the incidence of neural tube defects and may decrease the risk of Alzheimer and cardiovascular diseases and cancer. Hence, food fortification and intake of supplemental folate are widespread. OBJECTIVE: We examined the effects of long-term folate oversupplementation on the physiologic markers of intestinal and renal folate uptake processes. DESIGN:Human-derived intestinal Caco-2 and renal HK-2 epithelial cells were maintained (5 generations) in a growth medium oversupplemented (100 micromol folic acid/L) or maintained under sufficient conditions (0.25 and 9 micromol folic acid/L). RESULTS: Carrier-mediated uptake of (3)H-folic acid (2 micromol/L) at buffer pH 5.5 (but not buffer pH 7.4) by Caco-2 and HK-2 cells maintained under the folate-oversupplemented condition was significantly (P<0.01) and specifically lower than in cells maintained under the folate-sufficient condition. This reduction in folic acid uptake was associated with a significant decrease in the protein and mRNA levels of the human reduced-folate carrier (hRFC) and a decrease in the activity of the hRFC promoter. It was also associated with a decrease in mRNA levels of the proton-coupled folate transporter/heme carrier protein 1 (PCFT/HCP1) and folate receptor (FR). CONCLUSIONS: Long-term oversupplementation with folate leads to a specific and significant down-regulation in intestinal and renal folate uptake, which is associated with a decrease in message levels of hRFC, PCFT/HCP1, and FR. This regulation appears to be mediated via a transcriptional mechanism, at least for the hRFC system.
Authors: Sarah F Knight; Kousik Kundu; Giji Joseph; Sergey Dikalov; Daiana Weiss; Niren Murthy; W Robert Taylor Journal: J Am Soc Nephrol Date: 2012-01-26 Impact factor: 10.121
Authors: A Joan Levine; Jane C Figueiredo; Won Lee; David V Conti; Kathleen Kennedy; David J Duggan; Jenny N Poynter; Peter T Campbell; Polly Newcomb; Maria Elena Martinez; John L Hopper; Loic Le Marchand; John A Baron; Paul J Limburg; Cornelia M Ulrich; Robert W Haile Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-07 Impact factor: 4.254
Authors: Chandrika J Piyathilake; Maurizio Macaluso; Jorge E Celedonio; Suguna Badiga; Walter C Bell; William E Grizzle Journal: Int J Womens Health Date: 2010-08-09
Authors: Balasubramaniem Ashokkumar; Svetlana M Nabokina; Thomas Y Ma; Hamid M Said Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-07-01 Impact factor: 4.052