;PMID: 11932209 ;source_file_1895.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..40] = [t:0..40] ;1)sentence:[e:46..158] = [t:46..158] ;2)section:[e:162..212] = [t:162..212] ;3)section:[e:216..365] = [t:216..365] ;4)sentence:[e:369..538] = [t:369..538] ;5)sentence:[e:539..683] = [t:539..683] ;6)sentence:[e:684..821] = [t:684..821] ;7)sentence:[e:822..906] = [t:822..906] ;8)sentence:[e:908..1056] = [t:908..1056] ;9)sentence:[e:1057..1340] = [t:1057..1340] ;10)sentence:[e:1341..1491] = [t:1341..1491] ;11)sentence:[e:1492..1588] = [t:1492..1588] ;12)sentence:[e:1589..1676] = [t:1589..1676] ;13)sentence:[e:1677..1879] = [t:1677..1879] ;14)sentence:[e:1880..2001] = [t:1880..2001] ;15)sentence:[e:2002..2163] = [t:2002..2163] ;16)sentence:[e:2164..2371] = [t:2164..2371] ;17)sentence:[e:2372..2559] = [t:2372..2559] ;18)sentence:[e:2560..2792] = [t:2560..2792] ;19)sentence:[e:2793..2920] = [t:2793..2920] ;20)sentence:[e:2922..3022] = [t:2922..3022] ;21)section:[e:3026..3071] = [t:3026..3071] ;section 0 Span:0..40 ;J Mol Endocrinol. 2002 Apr;28(2):125-35. (SEC (FRAG (NNP:[0..1] J) (NNP:[2..5] Mol) (NNP:[6..16] Endocrinol) (.:[16..17] .) ('':[18..22] 2002) (CC:[23..30] Apr;28-LRB-) (CD:[30..31] 2) (-RRB-:[31..32] -RRB-) (::[32..33] :) (CD:[33..39] 125-35) (.:[39..40] .))) ;sentence 1 Span:46..158 ;Differential regulation of aldosterone synthase and 11beta-hydroxylase ;transcription by steroidogenic factor-1. ;[73..93]:cyp450:"aldosterone synthase" ;[98..116]:cyp450:"11beta-hydroxylase" ;[135..157]:substance:"steroidogenic factor-1" (SENT (NP (NP (JJ:[46..58] Differential) (NN:[59..69] regulation)) (PP (IN:[70..72] of) (NP (NP (NN:[73..84] aldosterone) (NN:[85..93] synthase)) (CC:[94..97] and) (NP (NN:[98..116] 11beta-hydroxylase) (NN:[118..131] transcription)))) (PP (IN:[132..134] by) (NP (JJ:[135..148] steroidogenic) (NN:[149..157] factor-1))) (.:[157..158] .))) ;section 2 Span:162..212 ;Bassett MH, Zhang Y, Clyne C, White PC, Rainey WE. (SEC (FRAG (NNP:[162..169] Bassett) (NN:[170..172] MH) (,:[172..173] ,) (NNP:[174..179] Zhang) (NNP:[180..181] Y) (,:[181..182] ,) (NNP:[183..188] Clyne) (NNP:[189..190] C) (,:[190..191] ,) (JJ:[192..197] White) (NN:[198..200] PC) (,:[200..201] ,) (NNP:[202..208] Rainey) (NNP:[209..212] WE.))) ;section 3 Span:216..365 ;Department of Obstetrics and Gynecology, University of Texas Southwestern ;Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9032, USA. (SEC (FRAG (NNP:[216..226] Department) (IN:[227..229] of) (NNP:[230..240] Obstetrics) (CC:[241..244] and) (NNP:[245..255] Gynecology) (,:[255..256] ,) (NNP:[257..267] University) (IN:[268..270] of) (NNP:[271..276] Texas) (NNP:[277..289] Southwestern) (NNP:[291..298] Medical) (NNP:[299..305] Center) (,:[305..306] ,) (CD:[307..311] 5323) (NNP:[312..317] Harry) (NNP:[318..323] Hines) (NNP:[324..333] Boulevard) (,:[333..334] ,) (NNP:[335..341] Dallas) (,:[341..342] ,) (NNP:[343..348] Texas) (CD:[349..354] 75390) (HYPH:[354..355] -) (CD:[355..359] 9032) (,:[359..360] ,) (NNP:[361..364] USA) (.:[364..365] .))) ;sentence 4 Span:369..538 ;11beta-Hydroxylase (hCYP11B1) and aldosterone synthase (hCYP11B2) are closely ; related isozymes with distinct roles in cortisol and aldosterone production ;respectively. ;[369..387]:cyp450:"11beta-Hydroxylase" ;[389..397]:cyp450:"hCYP11B1" ;[403..423]:cyp450:"aldosterone synthase" ;[425..433]:cyp450:"hCYP11B2" ;[456..464]:cyp450:"isozymes" ;[488..496]:substance:"cortisol" ;[501..512]:substance:"aldosterone" (SENT (S (NP-SBJ (NP (NP (NN:[369..387] 11beta-Hydroxylase)) (NP (-LRB-:[388..389] -LRB-) (NN:[389..397] hCYP11B1) (-RRB-:[397..398] -RRB-))) (CC:[399..402] and) (NP (NP (NN:[403..414] aldosterone) (NN:[415..423] synthase)) (NP (-LRB-:[424..425] -LRB-) (NN:[425..433] hCYP11B2) (-RRB-:[433..434] -RRB-)))) (VP (VBP:[435..438] are) (NP-PRD (NP (ADJP (RB:[439..446] closely) (VBN:[448..455] related)) (NNS:[456..464] isozymes)) (PP (IN:[465..469] with) (NP (NP (JJ:[470..478] distinct) (NNS:[479..484] roles)) (PP-LOC (IN:[485..487] in) (NP (NP (NN:[488..496] cortisol) (NML-1 (-NONE-:[496..496] *P*))) (CC:[497..500] and) (NP (NN:[501..512] aldosterone) (NML-1 (NN:[513..523] production))) (ADVP (RB:[525..537] respectively)))))))) (.:[537..538] .))) ;sentence 5 Span:539..683 ;Aldosterone synthase catalyzes the final step in aldosterone biosynthesis ;and is expressed only in the zona glomerulosa of the normal adrenal. ;[539..559]:cyp450:"Aldosterone synthase" ;[588..599]:substance:"aldosterone" (SENT (S (NP-SBJ-1 (NN:[539..550] Aldosterone) (NN:[551..559] synthase)) (VP (VP (VBZ:[560..569] catalyzes) (NP (NP (DT:[570..573] the) (JJ:[574..579] final) (NN:[580..584] step)) (PP (IN:[585..587] in) (NP (NN:[588..599] aldosterone) (NN:[601..613] biosynthesis))))) (CC:[614..617] and) (VP (VBZ:[618..620] is) (VP (VBN:[621..630] expressed) (NP-1 (-NONE-:[630..630] *)) (PP-LOC (ADVP (RB:[631..635] only)) (IN:[636..638] in) (NP (NP (DT:[639..642] the) (NN:[643..647] zona) (NN:[648..659] glomerulosa)) (PP (IN:[660..662] of) (NP (DT:[663..666] the) (JJ:[667..673] normal) (NN:[675..682] adrenal)))))))) (.:[682..683] .))) ;sentence 6 Span:684..821 ;11beta-Hydroxylase catalyzes the final reaction in the production of ;cortisol and is expressed at higher levels in the zona fasciculata. ;[684..702]:cyp450:"11beta-Hydroxylase" ;[754..762]:substance:"cortisol" (SENT (S (NP-SBJ-1 (NN:[684..702] 11beta-Hydroxylase)) (VP (VP (VBZ:[703..712] catalyzes) (NP (NP (DT:[713..716] the) (JJ:[717..722] final) (NN:[723..731] reaction)) (PP (IN:[732..734] in) (NP (NP (DT:[735..738] the) (NN:[739..749] production)) (PP (IN:[750..752] of) (NP (NN:[754..762] cortisol))))))) (CC:[763..766] and) (VP (VBZ:[767..769] is) (VP (VBN:[770..779] expressed) (NP-1 (-NONE-:[779..779] *)) (PP (IN:[780..782] at) (NP (JJR:[783..789] higher) (NNS:[790..796] levels))) (PP-LOC (IN:[797..799] in) (NP (DT:[800..803] the) (NN:[804..808] zona) (NN:[809..820] fasciculata)))))) (.:[820..821] .))) ;sentence 7 Span:822..906 ;The mechanisms causing differential expression of these genes are not well ;defined. (SENT (S (NP-SBJ-1 (NP (DT:[822..825] The) (NNS:[827..837] mechanisms)) (VP (VBG:[838..845] causing) (NP (NP (JJ:[846..858] differential) (NN:[859..869] expression)) (PP (IN:[870..872] of) (NP (DT:[873..878] these) (NNS:[879..884] genes)))))) (VP (VBP:[885..888] are) (RB:[889..892] not) (ADVP (RB:[893..897] well)) (VP (VBN:[898..905] defined) (NP-1 (-NONE-:[905..905] *)))) (.:[905..906] .))) ;sentence 8 Span:908..1056 ;Herein, we demonstrate contrasting roles for the orphan receptor ;steroidogenic factor-1 (SF-1) in the regulation of human (h) CYP11B1 and ;hCYP11B2. ;[964..972]:substance:"receptor" ;[973..996]:substance:"steroidogenic factor-1" ;[998..1002]:substance:"SF-1" ;[1025..1042]:cyp450:"human (h) CYP11B1" ;[1047..1055]:cyp450:"hCYP11B2" (SENT (S (ADVP-LOC (RB:[908..914] Herein)) (,:[914..915] ,) (NP-SBJ (PRP:[916..918] we)) (VP (VBP:[919..930] demonstrate) (NP (NP (VBG:[931..942] contrasting) (NNS:[943..948] roles)) (PP (IN:[949..952] for) (NP (NP (DT:[953..956] the) (NN:[957..963] orphan) (NN:[964..972] receptor)) (NP (NP (JJ:[973..986] steroidogenic) (NN:[988..996] factor-1)) (NP (-LRB-:[997..998] -LRB-) (NN:[998..1002] SF-1) (-RRB-:[1002..1003] -RRB-))))) (PP (IN:[1004..1006] in) (NP (NP (DT:[1007..1010] the) (NN:[1011..1021] regulation)) (PP (IN:[1022..1024] of) (NP (NP (NML (NML (JJ:[1025..1030] human)) (NML (-LRB-:[1031..1032] -LRB-) (JJ:[1032..1033] h) (-RRB-:[1033..1034] -RRB-))) (NN:[1035..1042] CYP11B1)) (CC:[1043..1046] and) (NP (NN:[1047..1055] hCYP11B2)))))))) (.:[1055..1056] .))) ;sentence 9 Span:1057..1340 ;Human NCI-H295R (H295R) or mouse Y-1 cells were transiently transfected with ; luciferase reporter constructs containing 5'-flanking regions of hCYP11B1, ;hCYP11B2, human 17alpha-hydroxylase (hCYP17), human cholesterol side-chain ;cleavage (hCYP11A1) or mouse (m) cyp11b2 (mcyp11b2). ;[1136..1146]:substance:"luciferase" ;[1147..1155]:substance:"reporter" ;[1201..1209]:cyp450:"hCYP11B1" ;[1212..1220]:cyp450:"hCYP11B2" ;[1222..1247]:cyp450:"human 17alpha-hydroxylase" ;[1249..1255]:cyp450:"hCYP17" ;[1258..1296]:cyp450:"human cholesterol side-chain cleavage" ;[1298..1306]:cyp450:"hCYP11A1" ;[1311..1328]:cyp450:"mouse (m) cyp11b2" ;[1330..1338]:cyp450:"mcyp11b2" (SENT (S (NP-SBJ-2 (NP (NML (NML (JJ:[1057..1062] Human) (NN:[1064..1073] NCI-H295R)) (NML (-LRB-:[1074..1075] -LRB-) (NN:[1075..1080] H295R) (-RRB-:[1080..1081] -RRB-))) (NML-1 (-NONE-:[1081..1081] *P*))) (CC:[1082..1084] or) (NP (NN:[1085..1090] mouse) (NN:[1091..1094] Y-1) (NML-1 (NNS:[1095..1100] cells)))) (VP (VBD:[1101..1105] were) (ADVP-MNR (RB:[1106..1117] transiently)) (VP (VBN:[1118..1129] transfected) (NP-2 (-NONE-:[1129..1129] *)) (PP (IN:[1130..1134] with) (NP (NP (NN:[1136..1146] luciferase) (NN:[1147..1155] reporter) (NNS:[1156..1166] constructs)) (VP (VBG:[1167..1177] containing) (NP (NP (NML (NML (CD:[1178..1179] 5) (SYM:[1179..1180] ')) (HYPH:[1180..1181] -) (NN:[1181..1189] flanking)) (NNS:[1190..1197] regions)) (PP (IN:[1198..1200] of) (NP (NP (NN:[1201..1209] hCYP11B1)) (,:[1209..1210] ,) (NP (NN:[1212..1220] hCYP11B2)) (,:[1220..1221] ,) (NP (NP (JJ:[1222..1227] human) (NN:[1228..1247] 17alpha-hydroxylase)) (NP (-LRB-:[1248..1249] -LRB-) (NN:[1249..1255] hCYP17) (-RRB-:[1255..1256] -RRB-))) (,:[1256..1257] ,) (NP (NP (JJ:[1258..1263] human) (NN:[1264..1275] cholesterol) (NML (NN:[1276..1280] side) (HYPH:[1280..1281] -) (NN:[1281..1286] chain)) (NN:[1288..1296] cleavage)) (NP (-LRB-:[1297..1298] -LRB-) (NN:[1298..1306] hCYP11A1) (-RRB-:[1306..1307] -RRB-))) (CC:[1308..1310] or) (NP (NP (NML (NML (NN:[1311..1316] mouse)) (NML (-LRB-:[1317..1318] -LRB-) (NN:[1318..1319] m) (-RRB-:[1319..1320] -RRB-))) (NN:[1321..1328] cyp11b2)) (NP (-LRB-:[1329..1330] -LRB-) (NN:[1330..1338] mcyp11b2) (-RRB-:[1338..1339] -RRB-))))))))))) (.:[1339..1340] .))) ;sentence 10 Span:1341..1491 ;Co-transfection of vectors encoding SF-1 increased expression of hCYP11B1, ;hCYP11A1 and hCYP17 constructs, but inhibited hCYP11B2 reporter activity. ;[1378..1382]:substance:"SF-1" ;[1407..1415]:cyp450:"hCYP11B1" ;[1417..1425]:cyp450:"hCYP11A1" ;[1430..1436]:cyp450:"hCYP17" ;[1464..1472]:cyp450:"hCYP11B2" ;[1473..1481]:substance:"reporter" (SENT (S (NP-SBJ (NP (AFX:[1341..1343] Co) (HYPH:[1343..1344] -) (NN:[1344..1356] transfection)) (PP (IN:[1357..1359] of) (NP (NP (NNS:[1360..1367] vectors)) (VP (VBG:[1369..1377] encoding) (NP (NN:[1378..1382] SF-1)))))) (VP (VP (VBD:[1383..1392] increased) (NP (NP (NN:[1393..1403] expression)) (PP (IN:[1404..1406] of) (NP (NP (NN:[1407..1415] hCYP11B1) (NML-1 (-NONE-:[1415..1415] *P*))) (,:[1415..1416] ,) (NP (NN:[1417..1425] hCYP11A1) (NML-1 (-NONE-:[1425..1425] *P*))) (CC:[1426..1429] and) (NP (NN:[1430..1436] hCYP17) (NML-1 (NNS:[1437..1447] constructs))))))) (,:[1447..1448] ,) (CC:[1450..1453] but) (VP (VBD:[1454..1463] inhibited) (NP (NN:[1464..1472] hCYP11B2) (NN:[1473..1481] reporter) (NN:[1482..1490] activity)))) (.:[1490..1491] .))) ;sentence 11 Span:1492..1588 ;Murine, bovine and human SF-1 were unable to increase transcription of ;hCYP11B2 in H295R cells. ;[1517..1521]:substance:"SF-1" ;[1564..1572]:cyp450:"hCYP11B2" (SENT (S (NP-SBJ-2 (NP (JJ:[1492..1498] Murine) (NML-1 (-NONE-:[1498..1498] *P*))) (,:[1498..1499] ,) (NP (JJ:[1500..1506] bovine) (NML-1 (-NONE-:[1506..1506] *P*))) (CC:[1507..1510] and) (NP (JJ:[1511..1516] human) (NML-1 (NN:[1517..1521] SF-1)))) (VP (VBD:[1522..1526] were) (ADJP-PRD (JJ:[1528..1534] unable) (S (NP-SBJ-2 (-NONE-:[1534..1534] *)) (VP (TO:[1535..1537] to) (VP (VB:[1538..1546] increase) (NP (NP (NN:[1547..1560] transcription)) (PP (IN:[1561..1563] of) (NP (NN:[1564..1572] hCYP11B2)))) (PP-LOC (IN:[1573..1575] in) (NP (NN:[1576..1581] H295R) (NNS:[1582..1587] cells)))))))) (.:[1587..1588] .))) ;sentence 12 Span:1589..1676 ;Both hCYP11B2 and mcyp11b2 promoter constructs were inhibited similarly by ;human SF-1. ;[1594..1602]:cyp450:"hCYP11B2" ;[1608..1616]:cyp450:"mcyp11b2" ;[1617..1625]:substance:"promoter" ;[1671..1675]:substance:"SF-1" (SENT (S (NP-SBJ-2 (CC:[1589..1593] Both) (NP (NN:[1594..1602] hCYP11B2) (NML-1 (-NONE-:[1602..1602] *P*))) (CC:[1603..1606] and) (NP (NN:[1608..1616] mcyp11b2) (NML-1 (NN:[1617..1625] promoter) (NNS:[1626..1636] constructs)))) (VP (VBD:[1637..1641] were) (VP (VBN:[1642..1651] inhibited) (NP-2 (-NONE-:[1651..1651] *)) (ADVP-MNR (RB:[1652..1661] similarly)) (PP (IN:[1662..1664] by) (NP-LGS (JJ:[1665..1670] human) (NN:[1671..1675] SF-1))))) (.:[1675..1676] .))) ;sentence 13 Span:1677..1879 ;In mouse Y-1 cells, reporter expression of hCYP11B2 and mcyp11b2 was very ;low compared with hCYP11B1 constructs, suggesting that this adrenal cell ;model may not be appropriate for studies of CYP11B2. ;[1698..1706]:substance:"reporter" ;[1721..1729]:cyp450:"hCYP11B2" ;[1734..1742]:cyp450:"mcyp11b2" ;[1771..1779]:cyp450:"hCYP11B1" ;[1871..1878]:cyp450:"CYP11B2" (SENT (S (PP-LOC (IN:[1677..1679] In) (NP (NN:[1680..1685] mouse) (NN:[1687..1690] Y-1) (NNS:[1691..1696] cells))) (,:[1696..1697] ,) (NP-SBJ (NP (NN:[1698..1706] reporter) (NN:[1707..1717] expression)) (PP (IN:[1718..1720] of) (NP (NN:[1721..1729] hCYP11B2) (CC:[1730..1733] and) (NN:[1734..1742] mcyp11b2)))) (VP (VBD:[1743..1746] was) (ADJP-PRD (RB:[1747..1751] very) (JJ:[1752..1755] low)) (S-ADV (NP-SBJ-1 (-NONE-:[1755..1755] *)) (VP (VBN:[1756..1764] compared) (NP-1 (-NONE-:[1764..1764] *)) (PP-CLR (IN:[1766..1770] with) (NP (NN:[1771..1779] hCYP11B1) (NNS:[1780..1790] constructs))))) (,:[1790..1791] ,) (S-ADV (NP-SBJ (-NONE-:[1791..1791] *)) (VP (VBG:[1792..1802] suggesting) (SBAR (IN:[1803..1807] that) (S (NP-SBJ (DT:[1808..1812] this) (JJ:[1813..1820] adrenal) (NN:[1821..1825] cell) (NN:[1826..1831] model)) (VP (MD:[1832..1835] may) (RB:[1836..1839] not) (VP (VB:[1840..1842] be) (ADJP-PRD (JJ:[1844..1855] appropriate) (PP (IN:[1856..1859] for) (NP (NP (NNS:[1860..1867] studies)) (PP (IN:[1868..1870] of) (NP (NN:[1871..1878] CYP11B2))))))))))))) (.:[1878..1879] .))) ;sentence 14 Span:1880..2001 ;Electrophoretic mobility shift assay demonstrated that SF-1 interacted with ;an element from both hCYP11B1 and hCYP11B2. ;[1936..1940]:substance:"SF-1" ;[1978..1986]:cyp450:"hCYP11B1" ;[1992..2000]:cyp450:"hCYP11B2" (SENT (S (NP-SBJ (NML (JJ:[1880..1895] Electrophoretic) (NN:[1896..1904] mobility) (NN:[1905..1910] shift)) (NN:[1911..1916] assay)) (VP (VBD:[1918..1930] demonstrated) (SBAR (IN:[1931..1935] that) (S (NP-SBJ (NN:[1936..1940] SF-1)) (VP (VBD:[1941..1951] interacted) (PP-CLR (IN:[1952..1956] with) (NP (NP (DT:[1957..1959] an) (NN:[1960..1967] element)) (PP (IN:[1968..1972] from) (NP (CC:[1973..1977] both) (NN:[1978..1986] hCYP11B1) (CC:[1987..1990] and) (NN:[1992..2000] hCYP11B2))))))))) (.:[2000..2001] .))) ;sentence 15 Span:2002..2163 ;However, mutation of this element, termed Ad4, did not prevent agonist ;stimulation of hCYP11B2 by angiotensin II or forskolin but blocked activity ;of hCYP11B1. ;[2065..2072]:substance:"agonist" ;[2089..2097]:cyp450:"hCYP11B2" ;[2101..2115]:substance:"angiotensin II" ;[2119..2128]:substance:"forskolin" ;[2154..2162]:cyp450:"hCYP11B1" (SENT (S (ADVP (RB:[2002..2009] However)) (,:[2009..2010] ,) (NP-SBJ (NP (NP (NN:[2011..2019] mutation)) (PP (IN:[2020..2022] of) (NP (DT:[2023..2027] this) (NN:[2028..2035] element)))) (,:[2035..2036] ,) (VP (VBN:[2037..2043] termed) (S (NP-SBJ (-NONE-:[2043..2043] *)) (NP-PRD (NN:[2044..2047] Ad4))))) (,:[2047..2048] ,) (VP (VP (VBD:[2049..2052] did) (RB:[2053..2056] not) (VP (VB:[2057..2064] prevent) (NP (NP (NN:[2065..2072] agonist) (NN:[2074..2085] stimulation)) (PP (IN:[2086..2088] of) (NP (NN:[2089..2097] hCYP11B2))) (PP (IN:[2098..2100] by) (NP (NP (NN:[2101..2112] angiotensin) (CD:[2113..2115] II)) (CC:[2116..2118] or) (NP (NN:[2119..2128] forskolin))))))) (CC:[2129..2132] but) (VP (VBD:[2133..2140] blocked) (NP (NP (NN:[2141..2149] activity)) (PP (IN:[2150..2152] of) (NP (NN:[2154..2162] hCYP11B1)))))) (.:[2162..2163] .))) ;sentence 16 Span:2164..2371 ;In some, but not all, reports of genetic linkage analysis, a naturally ;occurring single nucleotide polymorphism within the Ad4 element of hCYP11B2 ;(-344C/T) has been associated with cardiovascular disease. ;[2303..2311]:cyp450:"hCYP11B2" (SENT (S (PP-LOC (IN:[2164..2166] In) (NP (NP (DT:[2167..2171] some) (NP-2 (-NONE-:[2171..2171] *P*))) (,:[2171..2172] ,) (CONJP (CC:[2173..2176] but) (RB:[2177..2180] not)) (NP (DT:[2181..2184] all) (,:[2184..2185] ,) (NP-2 (NP (NNS:[2186..2193] reports)) (PP (IN:[2194..2196] of) (NP (NML (JJ:[2197..2204] genetic) (NN:[2205..2212] linkage)) (NN:[2213..2221] analysis))))))) (,:[2221..2222] ,) (NP-SBJ-1 (NP (DT:[2223..2224] a) (ADJP (RB:[2225..2234] naturally) (VBG:[2236..2245] occurring)) (NML (JJ:[2246..2252] single) (NN:[2253..2263] nucleotide)) (NN:[2264..2276] polymorphism)) (PP-LOC (IN:[2277..2283] within) (NP (NP (DT:[2284..2287] the) (NN:[2288..2291] Ad4) (NN:[2292..2299] element)) (PP (IN:[2300..2302] of) (NP (NP (NN:[2303..2311] hCYP11B2)) (PRN (-LRB-:[2313..2314] -LRB-) (NP (NML (SYM:[2314..2315] -) (CD:[2315..2318] 344)) (NN:[2318..2319] C)) (PP (SYM:[2319..2320] /) (NP (NN:[2320..2321] T))) (-RRB-:[2321..2322] -RRB-))))))) (VP (VBZ:[2323..2326] has) (VP (VBN:[2327..2331] been) (VP (VBN:[2332..2342] associated) (NP-1 (-NONE-:[2342..2342] *)) (PP-CLR (IN:[2343..2347] with) (NP (JJ:[2348..2362] cardiovascular) (NN:[2363..2370] disease)))))) (.:[2370..2371] .))) ;sentence 17 Span:2372..2559 ;Herein, we have demonstrated that this polymorphism influenced binding of ;SF-1 in electrophoretic mobility shift assays, with the C allele binding ;SF-1 more strongly than the T allele. ;[2447..2451]:substance:"SF-1" ;[2521..2525]:substance:"SF-1" (SENT (S (ADVP-LOC (RB:[2372..2378] Herein)) (,:[2378..2379] ,) (NP-SBJ (PRP:[2380..2382] we)) (VP (VBP:[2383..2387] have) (VP (VBN:[2389..2401] demonstrated) (SBAR (IN:[2402..2406] that) (S (NP-SBJ (DT:[2407..2411] this) (NN:[2412..2424] polymorphism)) (VP (VBD:[2425..2435] influenced) (NP (NP (NN:[2436..2443] binding)) (PP (IN:[2444..2446] of) (NP (NN:[2447..2451] SF-1)))) (PP (IN:[2452..2454] in) (NP (NML (JJ:[2456..2471] electrophoretic) (NN:[2472..2480] mobility) (NN:[2481..2486] shift)) (NNS:[2487..2493] assays))) (,:[2493..2494] ,) (PP (IN:[2495..2499] with) (S-NOM (NP-SBJ (DT:[2500..2503] the) (NN:[2504..2505] C) (NN:[2506..2512] allele)) (VP (VBG:[2513..2520] binding) (NP (NN:[2521..2525] SF-1)) (ADVP-MNR (ADVP (RBR:[2526..2530] more) (RB:[2532..2540] strongly)) (PP (IN:[2541..2545] than) (NP (DT:[2546..2549] the) (NN:[2550..2551] T) (NN:[2552..2558] allele)))))))))))) (.:[2558..2559] .))) ;sentence 18 Span:2560..2792 ;However, when hCYP11B2 constructs containing these alleles were transfected ;into H295R cells, there was no difference in agonist-stimulated expression ;or the response of either reporter construct to co-expression with human ;SF-1. ;[2574..2582]:cyp450:"hCYP11B2" ;[2683..2690]:substance:"agonist" ;[2739..2747]:substance:"reporter" ;[2787..2791]:substance:"SF-1" (SENT (S (ADVP (RB:[2560..2567] However)) (,:[2567..2568] ,) (SBAR-ADV (WHADVP-3 (WRB:[2569..2573] when)) (S (NP-SBJ-1 (NP (NN:[2574..2582] hCYP11B2) (NNS:[2583..2593] constructs)) (VP (VBG:[2594..2604] containing) (NP (DT:[2605..2610] these) (NNS:[2612..2619] alleles)))) (VP (VBD:[2620..2624] were) (VP (VBN:[2625..2636] transfected) (NP-1 (-NONE-:[2636..2636] *)) (PP-LOC (IN:[2637..2641] into) (NP (NN:[2642..2647] H295R) (NNS:[2648..2653] cells))) (ADVP-TMP-3 (-NONE-:[2653..2653] *T*)))))) (,:[2653..2654] ,) (NP-SBJ (EX:[2655..2660] there)) (VP (VBD:[2661..2664] was) (NP-PRD (NP (DT:[2665..2667] no) (NN:[2668..2678] difference)) (PP (IN:[2679..2681] in) (NP (NP (ADJP (NN:[2683..2690] agonist) (HYPH:[2690..2691] -) (VBN:[2691..2701] stimulated)) (NN:[2702..2712] expression)) (CC:[2713..2715] or) (NP (NP (DT:[2716..2719] the) (NN:[2720..2728] response)) (PP (IN:[2729..2731] of) (NP (DT:[2732..2738] either) (NN:[2739..2747] reporter) (NN:[2748..2757] construct))) (PP (TO:[2758..2760] to) (NP (NP (AFX:[2762..2764] co) (HYPH:[2764..2765] -) (NN:[2765..2775] expression)) (PP (IN:[2776..2780] with) (NP (JJ:[2781..2786] human) (NN:[2787..2791] SF-1)))))))))) (.:[2791..2792] .))) ;sentence 19 Span:2793..2920 ;Taken together, these data suggest that SF-1 and the Ad4 element are not ;major regulators of adrenal hCYP11B2 gene expression. ;[2833..2837]:substance:"SF-1" ;[2873..2883]:substance:"regulators" ;[2895..2903]:cyp450:"hCYP11B2" (SENT (S (S-ADV (NP-SBJ (-NONE-:[2793..2793] *)) (VP (VBN:[2793..2798] Taken) (ADVP (RB:[2799..2807] together)))) (,:[2807..2808] ,) (NP-SBJ (DT:[2809..2814] these) (NNS:[2815..2819] data)) (VP (VBP:[2820..2827] suggest) (SBAR (IN:[2828..2832] that) (S (NP-SBJ (NP (NN:[2833..2837] SF-1)) (CC:[2838..2841] and) (NP (DT:[2843..2846] the) (NN:[2847..2850] Ad4) (NN:[2851..2858] element))) (VP (VBP:[2859..2862] are) (RB:[2863..2866] not) (NP-PRD (NP (JJ:[2867..2872] major) (NNS:[2873..2883] regulators)) (PP (IN:[2884..2886] of) (NP (JJ:[2887..2894] adrenal) (NN:[2895..2903] hCYP11B2) (NN:[2904..2908] gene) (NN:[2909..2919] expression)))))))) (.:[2919..2920] .))) ;sentence 20 Span:2922..3022 ;Thus far, hCYP11B2 is the first steroid hydroxylase gene which is not ;positively regulated by SF-1. ;[2932..2940]:cyp450:"hCYP11B2" ;[2954..2973]:substance:"steroid hydroxylase" ;[3017..3021]:substance:"SF-1" (SENT (S (ADVP (RB:[2922..2926] Thus) (RB:[2927..2930] far)) (,:[2930..2931] ,) (NP-SBJ (NN:[2932..2940] hCYP11B2)) (VP (VBZ:[2941..2943] is) (NP-PRD (NP (DT:[2944..2947] the) (JJ:[2948..2953] first) (NML (NN:[2954..2961] steroid) (NN:[2962..2973] hydroxylase)) (NN:[2974..2978] gene)) (SBAR (WHNP-1 (WDT:[2979..2984] which)) (S (NP-SBJ-1 (-NONE-:[2984..2984] *T*)) (VP (VBZ:[2985..2987] is) (RB:[2988..2991] not) (ADVP (RB:[2992..3002] positively)) (VP (VBN:[3004..3013] regulated) (NP-1 (-NONE-:[3013..3013] *)) (PP (IN:[3014..3016] by) (NP-LGS (NN:[3017..3021] SF-1))))))))) (.:[3021..3022] .))) ;section 21 Span:3026..3071 ;PMID: 11932209 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[3026..3030] PMID) (::[3030..3031] :) (CD:[3032..3040] 11932209) (-LRB-:[3041..3042] -LSB-) (NNP:[3042..3048] PubMed) (HYPH:[3049..3050] -) (NN:[3051..3058] indexed) (IN:[3059..3062] for) (NNP:[3063..3070] MEDLINE) (-RRB-:[3070..3071] -RSB-)))