;PMID: 2351099 ;source_file_1893.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..39] = [t:0..39] ;1)sentence:[e:45..120] = [t:45..120] ;2)sentence:[e:121..175] = [t:121..175] ;3)section:[e:179..211] = [t:179..211] ;4)section:[e:215..320] = [t:215..320] ;5)sentence:[e:324..450] = [t:324..450] ;6)sentence:[e:451..600] = [t:451..600] ;7)sentence:[e:601..852] = [t:601..852] ;8)sentence:[e:853..1051] = [t:853..1051] ;9)sentence:[e:1052..1216] = [t:1052..1216] ;10)sentence:[e:1217..1307] = [t:1217..1307] ;11)sentence:[e:1308..1467] = [t:1308..1467] ;12)sentence:[e:1468..1571] = [t:1468..1571] ;13)sentence:[e:1572..1804] = [t:1572..1804] ;14)sentence:[e:1805..2020] = [t:1805..2020] ;15)section:[e:2024..2068] = [t:2024..2068] ;section 0 Span:0..39 ;Endocrinology. 1990 Jun;126(6):2868-75. (SEC (FRAG (NNP:[0..13] Endocrinology) (,:[13..14] .) (CD:[15..19] 1990) (.:[20..27] Jun;126) (-LRB-:[27..28] -LRB-) (CD:[28..29] 6) (-RRB-:[29..30] -RRB-) (::[30..31] :) (CD:[31..35] 2868) (HYPH:[35..36] -) (CD:[36..38] 75) (.:[38..39] .))) ;sentence 1 Span:45..120 ;Expression of 25-hydroxyvitamin D3-24-hydroxylase activity in Caco-2 cells. ;[59..94]:substance:"25-hydroxyvitamin D3-24-hydroxylase" (SENT (NP-HLN (NP (NN:[45..55] Expression)) (PP (IN:[56..58] of) (NP (NN:[59..76] 25-hydroxyvitamin) (NN:[77..94] D3-24-hydroxylase) (NN:[95..103] activity))) (PP-LOC (IN:[104..106] in) (NP (NN:[107..113] Caco-2) (NNS:[114..119] cells))) (.:[119..120] .))) ;sentence 2 Span:121..175 ;An in vitro model of intestinal vitamin D catabolism. ;[154..163]:substance:"vitamin D" (SENT (NP-HLN (NP (DT:[121..123] An) (ADJP (FW:[125..127] in) (FW:[128..133] vitro)) (NN:[134..139] model)) (PP (IN:[140..142] of) (NP (JJ:[143..153] intestinal) (NML (NN:[154..161] vitamin) (NN:[162..163] D)) (NN:[164..174] catabolism))) (.:[174..175] .))) ;section 3 Span:179..211 ;Tomon M, Tenenhouse HS, Jones G. (SEC (FRAG (NNP:[179..184] Tomon) (NNP:[185..187] M,) (NNP:[188..198] Tenenhouse) (NNP:[199..201] HS) (,:[201..202] ,) (NNP:[203..208] Jones) (NNP:[209..211] G.))) ;section 4 Span:215..320 ;Medical Research Council Genetics Group, McGill University-Montreal ;Children's Hospital, Quebec, Canada. (SEC (FRAG (NNP:[215..222] Medical) (NNP:[223..231] Research) (NNP:[232..239] Council) (NNP:[240..248] Genetics) (NNP:[249..254] Group) (,:[254..255] ,) (NNP:[256..262] McGill) (NNP:[263..282] University-Montreal) (NNP:[283..291] Children) (POS:[291..293] 's) (NNP:[295..303] Hospital) (,:[303..304] ,) (NNP:[305..311] Quebec) (,:[311..312] ,) (NNP:[313..319] Canada) (.:[319..320] .))) ;sentence 5 Span:324..450 ;The C-24 oxidation pathway plays a major role in the degradation of vitamin D ; metabolites in kidney and other target tissues. ;[392..414]:substance:"vitamin D metabolites" (SENT (S (NP-SBJ (DT:[324..327] The) (NN:[328..332] C-24) (NN:[333..342] oxidation) (NN:[343..350] pathway)) (VP (VBZ:[351..356] plays) (NP (DT:[357..358] a) (JJ:[359..364] major) (NN:[365..369] role)) (PP (IN:[370..372] in) (NP (NP (DT:[373..376] the) (NN:[377..388] degradation)) (PP (IN:[389..391] of) (NP (NML (NN:[392..399] vitamin) (NN:[400..401] D)) (NNS:[403..414] metabolites))) (PP (IN:[415..417] in) (NP (NP (NN:[418..424] kidney) (NML-1 (-NONE-:[424..424] *P*))) (CC:[425..428] and) (NP (JJ:[429..434] other) (NN:[435..441] target) (NML-1 (NNS:[442..449] tissues)))))))) (.:[449..450] .))) ;sentence 6 Span:451..600 ;The aim of the present study was to establish an intestinal cell culture ;system to study the mechanisms regulating the vitamin D catabolic pathway. ;[572..581]:substance:"vitamin D" (SENT (S (NP-SBJ (NP (DT:[451..454] The) (NN:[455..458] aim)) (PP (IN:[459..461] of) (NP (DT:[462..465] the) (JJ:[466..473] present) (NN:[474..479] study)))) (VP (VBD:[480..483] was) (S-PRP-PRD (NP-SBJ (-NONE-:[483..483] *)) (VP (TO:[485..487] to) (VP (VB:[488..497] establish) (NP (DT:[498..500] an) (JJ:[501..511] intestinal) (NML (NN:[512..516] cell) (NN:[517..524] culture)) (NN:[525..531] system)) (S-PRP (NP-SBJ (-NONE-:[531..531] *)) (VP (TO:[532..534] to) (VP (VB:[535..540] study) (NP (NP (DT:[541..544] the) (NNS:[545..555] mechanisms)) (VP (VBG:[557..567] regulating) (NP (DT:[568..571] the) (NML (NN:[572..579] vitamin) (NN:[580..581] D)) (JJ:[582..591] catabolic) (NN:[592..599] pathway))))))))))) (.:[599..600] .))) ;sentence 7 Span:601..852 ;25-Hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in ;the catabolic sequence, was examined in Caco-2 cells, a human colon ;adenocarcinoma cell line which exhibits differentiated functions of ;absorbing intestinal epithelial cells. ;[601..636]:cyp450:"25-Hydroxyvitamin D3-24-hydroxylase" ;[639..653]:cyp450:"24-hydroxylase" ;[666..672]:cyp450:"enzyme" (SENT (S (NP-SBJ-2 (NP (NP (NN:[601..618] 25-Hydroxyvitamin) (NN:[619..636] D3-24-hydroxylase)) (NP (-LRB-:[638..639] -LRB-) (NN:[639..653] 24-hydroxylase) (-RRB-:[653..654] -RRB-))) (,:[654..655] ,) (NP (NP (DT:[656..659] the) (JJ:[660..665] first) (NN:[666..672] enzyme)) (PP (IN:[673..675] in) (NP (DT:[676..679] the) (JJ:[680..689] catabolic) (NN:[690..698] sequence))))) (,:[698..699] ,) (VP (VBD:[700..703] was) (VP (VBN:[704..712] examined) (NP-2 (-NONE-:[712..712] *)) (PP-LOC (IN:[713..715] in) (NP (NP (NN:[717..723] Caco-2) (NNS:[724..729] cells)) (,:[729..730] ,) (NP (NP (DT:[731..732] a) (JJ:[733..738] human) (NN:[739..744] colon) (NN:[745..759] adenocarcinoma) (NN:[760..764] cell) (NN:[765..769] line)) (SBAR (WHNP-1 (WDT:[770..775] which)) (S (NP-SBJ-1 (-NONE-:[775..775] *T*)) (VP (VBZ:[776..784] exhibits) (NP (NP (VBN:[786..800] differentiated) (NNS:[801..810] functions)) (PP (IN:[811..813] of) (S-NOM (NP-SBJ (-NONE-:[813..813] *)) (VP (VBG:[814..823] absorbing) (NP (JJ:[824..834] intestinal) (JJ:[835..845] epithelial) (NNS:[846..851] cells)))))))))))))) (.:[851..852] .))) ;sentence 8 Span:853..1051 ;While untreated Caco-2 cells did not exhibit 24-hydroxylase activity, ;significant catabolic activity was induced by prior treatment of cell ;monolayers with 1,25-dihydroxyvitamin D3(1,25-(OH)2D3). ;[899..913]:cyp450:"24-hydroxylase" ;[1012..1036]:substance:"1,25-dihydroxyvitamin D3" ;[1037..1049]:substance:"1,25-(OH)2D3" (SENT (S (SBAR-ADV (IN:[853..858] While) (S (NP-SBJ (JJ:[860..869] untreated) (NN:[870..876] Caco-2) (NNS:[877..882] cells)) (VP (VBD:[883..886] did) (RB:[887..890] not) (VP (VB:[891..898] exhibit) (NP (NN:[899..913] 24-hydroxylase) (NN:[914..922] activity)))))) (,:[922..923] ,) (NP-SBJ-1 (JJ:[924..935] significant) (JJ:[937..946] catabolic) (NN:[947..955] activity)) (VP (VBD:[956..959] was) (VP (VBN:[960..967] induced) (NP-1 (-NONE-:[967..967] *)) (PP (IN:[968..970] by) (NP-LGS (NP (JJ:[971..976] prior) (NN:[977..986] treatment)) (PP (IN:[987..989] of) (NP (NN:[990..994] cell) (NNS:[995..1005] monolayers))) (PP (IN:[1006..1010] with) (NP (NP (NN:[1012..1033] 1,25-dihydroxyvitamin) (NN:[1034..1036] D3)) (NP (-LRB-:[1036..1037] -LRB-) (NN:[1037..1049] 1,25--LRB-OH-RRB-2D3) (-RRB-:[1049..1050] -RRB-)))))))) (.:[1050..1051] .))) ;sentence 9 Span:1052..1216 ;Induced 24-hydroxylase D3 (25OHD3) and 1,25-(OH)2D3 was detected 6 h after ;treatment of cells with 10(-8)M 1,25-(OH)2D3, peaked at 16 h, and decreased ;thereafter. ;[1060..1077]:cyp450:"24-hydroxylase D3" ;[1079..1085]:cyp450:"25OHD3" ;[1092..1104]:substance:"1,25-(OH)2D3" ;[1118..1119]:quantitative-value:"6" ;[1120..1121]:quantitative-units:"h" ;[1152..1158]:quantitative-value:"10(-8)" ;[1158..1159]:quantitative-units:"M" ;[1161..1173]:substance:"1,25-(OH)2D3" ;[1185..1187]:quantitative-value:"16" ;[1188..1189]:quantitative-units:"h" (SENT (S (NP-SBJ-2 (NP (NP (ADJP-1 (VBN:[1052..1059] Induced)) (NN:[1060..1074] 24-hydroxylase) (NN:[1075..1077] D3)) (NP (-LRB-:[1078..1079] -LRB-) (NN:[1079..1085] 25OHD3) (-RRB-:[1085..1086] -RRB-))) (CC:[1087..1090] and) (NP (ADJP-1 (-NONE-:[1090..1090] *P*)) (NN:[1092..1104] 1,25--LRB-OH-RRB-2D3))) (VP (VP (VBD:[1105..1108] was) (VP (VBN:[1109..1117] detected) (NP-2 (-NONE-:[1117..1117] *)) (PP-TMP (NP-ADV (CD:[1118..1119] 6) (NN:[1120..1121] h)) (IN:[1122..1127] after) (NP (NP (NN:[1128..1137] treatment)) (PP (IN:[1138..1140] of) (NP (NNS:[1141..1146] cells))) (PP (IN:[1147..1151] with) (NP (CD:[1152..1158] 10-LRB--8-RRB-) (NN:[1158..1159] M) (NN:[1161..1173] 1,25--LRB-OH-RRB-2D3)))))) (,:[1173..1174] ,)) (VP (VBD:[1175..1181] peaked) (PP-TMP (IN:[1182..1184] at) (NP (CD:[1185..1187] 16) (NN:[1188..1189] h)))) (,:[1189..1190] ,) (CC:[1191..1194] and) (VP (VBD:[1195..1204] decreased) (ADVP (RB:[1205..1215] thereafter)))) (.:[1215..1216] .))) ;sentence 10 Span:1217..1307 ;Treatment of cells with 10(-7) M 1,25-(OH)2D3 elicited a maximal ;24-hydroxylase response. ;[1242..1248]:quantitative-value:"10(-7)" ;[1249..1250]:quantitative-units:"M" ;[1251..1263]:quantitative-value:"1,25-(OH)2D3" ;[1283..1297]:cyp450:"24-hydroxylase" (SENT (S (NP-SBJ (NP (NN:[1217..1226] Treatment)) (PP (IN:[1227..1229] of) (NP (NNS:[1230..1235] cells))) (PP (IN:[1236..1240] with) (NP (NML (CD:[1242..1248] 10-LRB--7-RRB-) (NN:[1249..1250] M)) (NN:[1251..1263] 1,25--LRB-OH-RRB-2D3)))) (VP (VBD:[1264..1272] elicited) (NP (DT:[1273..1274] a) (JJ:[1275..1282] maximal) (NN:[1283..1297] 24-hydroxylase) (NN:[1298..1306] response))) (.:[1306..1307] .))) ;sentence 11 Span:1308..1467 ;Comparable time courses of induction by 1,25-(OH)2D3 and 1,25-(OH)2D3-dose ;response curves were observed in cultured human skin fibroblasts and Caco-2 ;cells. ;[1349..1361]:substance:"1,25-(OH)2D3" ;[1366..1378]:substance:"1,25-(OH)2D3" (SENT (S (NP-SBJ-4 (NP (JJ:[1308..1318] Comparable) (NN:[1320..1324] time) (NNS:[1325..1332] courses)) (PP (IN:[1333..1335] of) (NP (NP (NN:[1336..1345] induction)) (PP (IN:[1346..1348] by) (NP (NP (NML (NN:[1349..1361] 1,25--LRB-OH-RRB-2D3) (NML-3 (-NONE-:[1361..1361] *P*))) (NML-5 (-NONE-:[1361..1361] *P*))) (CC:[1362..1365] and) (NP (NML (NN:[1366..1378] 1,25--LRB-OH-RRB-2D3) (NML-3 (HYPH:[1378..1379] -) (NN:[1379..1383] dose))) (NML-5 (NN:[1384..1392] response) (NNS:[1393..1399] curves)))))))) (VP (VBD:[1401..1405] were) (VP (VBN:[1406..1414] observed) (NP-4 (-NONE-:[1414..1414] *)) (PP-LOC (IN:[1415..1417] in) (NP (NP (ADJP-1 (VBN:[1418..1426] cultured)) (ADJP-2 (JJ:[1427..1432] human)) (NN:[1433..1437] skin) (NNS:[1438..1449] fibroblasts)) (CC:[1450..1453] and) (NP (ADJP-1 (-NONE-:[1453..1453] *P*)) (ADJP-2 (-NONE-:[1453..1453] *P*)) (NN:[1454..1460] Caco-2) (NNS:[1461..1466] cells)))))) (.:[1466..1467] .))) ;sentence 12 Span:1468..1571 ;25OHD3 was not as good an inducer of the vitamin D catabolic pathway in ;Caco-2 cells as 1,25-(OH)2D3. ;[1468..1474]:cyp450:"25OHD3" ;[1510..1519]:substance:"vitamin D" ;[1558..1570]:substance:"1,25-(OH)2D3" (SENT (S (NP-SBJ (NN:[1468..1474] 25OHD3)) (VP (VBD:[1475..1478] was) (RB:[1480..1483] not) (NP-PRD (NP (ADJP (ADJP (RB:[1484..1486] as) (JJ:[1487..1491] good)) (PP-1 (-NONE-:[1491..1491] *ICH*))) (DT:[1492..1494] an) (NN:[1495..1502] inducer)) (PP (IN:[1503..1505] of) (NP (DT:[1506..1509] the) (NML (NN:[1510..1517] vitamin) (NN:[1518..1519] D)) (JJ:[1520..1529] catabolic) (NN:[1530..1537] pathway)))) (PP-LOC (IN:[1538..1540] in) (NP (NN:[1541..1547] Caco-2) (NNS:[1548..1553] cells))) (PP-1 (IN:[1554..1556] as) (NP (NN:[1558..1570] 1,25--LRB-OH-RRB-2D3)))) (.:[1570..1571] .))) ;sentence 13 Span:1572..1804 ;Induction of 24-hydroxylase activity by 1,25-(OH)2D3 was inhibited by ;pretreatment of Caco-2 cells with either actinomycin D, alpha-amanitin, or ;cycloheximide suggesting that mRNA and protein synthesis are required for ;induction. ;[1585..1599]:cyp450:"24-hydroxylase" ;[1612..1624]:substance:"1,25-(OH)2D3" ;[1684..1697]:substance:"actinomycin D" ;[1699..1713]:substance:"alpha-amanitin" ;[1719..1732]:substance:"cycloheximide" ;[1749..1753]:substance:"mRNA" ;[1758..1765]:substance:"protein" (SENT (S (NP-SBJ-3 (NP (NN:[1572..1581] Induction)) (PP (IN:[1582..1584] of) (NP (NN:[1585..1599] 24-hydroxylase) (NN:[1600..1608] activity))) (PP (IN:[1609..1611] by) (NP (NN:[1612..1624] 1,25--LRB-OH-RRB-2D3)))) (VP (VBD:[1625..1628] was) (VP (VBN:[1629..1638] inhibited) (NP-3 (-NONE-:[1638..1638] *)) (PP (IN:[1640..1642] by) (NP-LGS (NP (NN:[1643..1655] pretreatment)) (PP (IN:[1656..1658] of) (NP (NN:[1659..1665] Caco-2) (NNS:[1666..1671] cells))) (PP (IN:[1672..1676] with) (NP (CC:[1677..1683] either) (NP (NN:[1684..1695] actinomycin) (NN:[1696..1697] D)) (,:[1697..1698] ,) (NP (NN:[1699..1713] alpha-amanitin)) (,:[1713..1714] ,) (CC:[1715..1717] or) (NP (NN:[1719..1732] cycloheximide)))))) (S-MNR (NP-SBJ (-NONE-:[1732..1732] *)) (VP (VBG:[1733..1743] suggesting) (SBAR (IN:[1744..1748] that) (S (NP-SBJ-2 (NP (NN:[1749..1753] mRNA) (NML-1 (-NONE-:[1753..1753] *P*))) (CC:[1754..1757] and) (NP (NN:[1758..1765] protein) (NML-1 (NN:[1766..1775] synthesis)))) (VP (VBP:[1776..1779] are) (VP (VBN:[1780..1788] required) (NP-2 (-NONE-:[1788..1788] *)) (PP (IN:[1789..1792] for) (NP (NN:[1794..1803] induction))))))))))) (.:[1803..1804] .))) ;sentence 14 Span:1805..2020 ;The present study demonstrates that 1,25-(OH)2D3-treated Caco-2 cells ;express the vitamin D catabolic pathway and, therefore, constitute a useful ;in vitro model to study the mechanism of induction by 1,25-(OH)2D3. ;[1841..1853]:substance:"1,25-(OH)2D3" ;[1888..1897]:substance:"vitamin D" ;[2007..2019]:substance:"1,25-(OH)2D3" (SENT (S (NP-SBJ (DT:[1805..1808] The) (JJ:[1809..1816] present) (NN:[1817..1822] study)) (VP (VBZ:[1823..1835] demonstrates) (SBAR (IN:[1836..1840] that) (S (NP-SBJ (ADJP (NN:[1841..1853] 1,25--LRB-OH-RRB-2D3) (HYPH:[1853..1854] -) (VBN:[1854..1861] treated)) (NN:[1862..1868] Caco-2) (NNS:[1869..1874] cells)) (VP (VP (VBP:[1876..1883] express) (NP (DT:[1884..1887] the) (NML (NN:[1888..1895] vitamin) (NN:[1896..1897] D)) (JJ:[1898..1907] catabolic) (NN:[1908..1915] pathway))) (CC:[1916..1919] and) (,:[1919..1920] ,) (VP (ADVP (RB:[1921..1930] therefore)) (,:[1930..1931] ,) (VBP:[1932..1942] constitute) (NP (DT:[1943..1944] a) (JJ:[1945..1951] useful) (ADJP (FW:[1952..1954] in) (FW:[1956..1961] vitro)) (NN:[1962..1967] model)) (S-ADV (NP-SBJ (-NONE-:[1967..1967] *)) (VP (TO:[1968..1970] to) (VP (VB:[1971..1976] study) (NP (NP (DT:[1977..1980] the) (NN:[1981..1990] mechanism)) (PP (IN:[1991..1993] of) (NP (NP (NN:[1994..2003] induction)) (PP (IN:[2004..2006] by) (NP (NN:[2007..2019] 1,25--LRB-OH-RRB-2D3)))))))))))))) (.:[2019..2020] .))) ;section 15 Span:2024..2068 ;PMID: 2351099 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[2024..2028] PMID) (::[2028..2029] :) (CD:[2030..2037] 2351099) (NN:[2038..2039] -LSB-) (NNP:[2039..2045] PubMed) (::[2046..2047] -) (NN:[2048..2055] indexed) (IN:[2056..2059] for) (NNP:[2060..2068] MEDLINE-RSB-)))