Vitamin A up-regulates expression of bone-type alkaline phosphatase in rat small intestinal crypt cell line and fetal rat small intestine.
Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver-type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARbeta mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells.
Nikawa
T
T
Department of Nutrition, School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan.
Rokutan
K
K
Nanba
K
K
Tokuoka
K
K
Teshima
S
S
Engle
M J
MJ
Alpers
D H
DH
Kishi
K
K
D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D001842:Bone and Bones / Q000201:enzymology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004224:Diterpenes; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007421:Intestine, Small / Q000196:embryology* / Q000201:enzymology*; D007527:Isoenzymes / Q000235:genetics*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors; D000084562:Retinyl Esters; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014801:Vitamin A / Q000031:analogs & derivatives / Q000494:pharmacology*
D004224:Diterpenes; D007527:Isoenzymes; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D000084562:Retinyl Esters; D014157:Transcription Factors; D014801:Vitamin A; C009166:retinol acetate; D000469:Alkaline Phosphatase