;PMID: 9756946 ;source_file_1779.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..41] = [t:0..41] ;1)sentence:[e:47..120] = [t:47..120] ;2)sentence:[e:122..164] = [t:122..164] ;3)section:[e:168..187] = [t:168..187] ;4)section:[e:191..289] = [t:191..289] ;5)sentence:[e:293..396] = [t:293..396] ;6)sentence:[e:397..522] = [t:397..522] ;7)sentence:[e:524..702] = [t:524..702] ;8)sentence:[e:703..841] = [t:703..841] ;9)sentence:[e:842..966] = [t:842..966] ;10)sentence:[e:967..1040] = [t:967..1040] ;11)sentence:[e:1041..1225] = [t:1041..1225] ;12)sentence:[e:1226..1368] = [t:1226..1368] ;13)sentence:[e:1370..1452] = [t:1370..1452] ;14)sentence:[e:1453..1556] = [t:1453..1556] ;15)sentence:[e:1557..1617] = [t:1557..1617] ;16)sentence:[e:1618..1699] = [t:1618..1699] ;17)section:[e:1703..1747] = [t:1703..1747] ;section 0 Span:0..41 ;J Biol Chem. 1998 Oct 9;273(41):26969-76. (SEC (FRAG (NNP:[0..1] J) (NNP:[2..6] Biol) (NNP:[7..11] Chem) (.:[11..12] .) (CD:[13..17] 1998) (NNP:[18..21] Oct) (CD:[22..27] 9;273) (-LRB-:[27..28] -LRB-) (CD:[28..30] 41) (-RRB-:[30..31] -RRB-) (::[31..32] :) (CD:[32..37] 26969) (::[37..38] -) (CD:[38..40] 76) (.:[40..41] .))) ;sentence 1 Span:47..120 ;Down-regulation of cytochrome P450 1A1 gene promoter by oxidative stress. ;[66..85]:cyp450:"cytochrome P450 1A1" ;[91..99]:substance:"promoter" (SENT (NP-HLN (NP (RP:[47..51] Down) (HYPH:[51..52] -) (NN:[52..62] regulation)) (PP (IN:[63..65] of) (NP (NML (NML (NN:[66..76] cytochrome) (NN:[77..81] P450)) (NN:[82..85] 1A1)) (NN:[86..90] gene) (NN:[91..99] promoter))) (PP (IN:[100..102] by) (NP (JJ:[103..112] oxidative) (NN:[113..119] stress))) (.:[119..120] .))) ;sentence 2 Span:122..164 ;Critical contribution of nuclear factor 1. ;[147..163]:substance:"nuclear factor 1" (SENT (NP-HLN (NP (JJ:[122..130] Critical) (NN:[131..143] contribution)) (PP (IN:[144..146] of) (NP (JJ:[147..154] nuclear) (NN:[155..161] factor) (CD:[162..163] 1))) (.:[163..164] .))) ;section 3 Span:168..187 ;Morel Y, Barouki R. (SEC (FRAG (NNP:[168..173] Morel) (NNP:[174..175] Y) (,:[175..176] ,) (NNP:[177..184] Barouki) (NNP:[185..187] R.))) ;section 4 Span:191..289 ;INSERM U490, Centre Universitaire des Saints-Peres, 45 rue des Saints-Peres, ;75006 Paris, France. (SEC (FRAG (NNP:[191..197] INSERM) (CD:[198..202] U490) (,:[202..203] ,) (NNP:[204..210] Centre) (NNP:[211..224] Universitaire) (NNP:[225..228] des) (NNP:[229..235] Saints) (HYPH:[235..236] -) (NNP:[236..241] Peres) (,:[241..242] ,) (CD:[243..245] 45) (NNS:[246..249] rue) (VBZ:[250..253] des) (NNP:[254..260] Saints) (HYPH:[260..261] -) (NNP:[261..266] Peres) (,:[266..267] ,) (CD:[269..274] 75006) (NNP:[275..280] Paris) (,:[280..281] ,) (NNP:[282..288] France) (.:[288..289] .))) ;sentence 5 Span:293..396 ;Oxidative stress interferes with several cellular functions, in particular ;transcriptional regulation. (SENT (S (NP-SBJ (JJ:[293..302] Oxidative) (NN:[303..309] stress)) (VP (VBZ:[310..320] interferes) (PP-CLR (IN:[321..325] with) (NP (NP (JJ:[326..333] several) (JJ:[334..342] cellular) (NNS:[343..352] functions)) (,:[352..353] ,) (PP (IN:[354..356] in) (PP (JJ:[357..367] particular) (NP (JJ:[369..384] transcriptional) (NN:[385..395] regulation))))))) (.:[395..396] .))) ;sentence 6 Span:397..522 ;We show here that the human cytochrome P450 1A1 (CYP1A1) is down-regulated ;at the transcriptional level by oxidative stress. ;[425..444]:cyp450:"cytochrome P450 1A1" ;[447..453]:cyp450:"CYP1A1" (SENT (S (NP-SBJ (PRP:[397..399] We)) (VP (VBP:[400..404] show) (ADVP (RB:[405..409] here)) (SBAR (IN:[410..414] that) (S (NP-SBJ-1 (NP (DT:[415..418] the) (JJ:[419..424] human) (NN:[425..435] cytochrome) (NN:[436..440] P450) (NN:[441..444] 1A1)) (NP (-LRB-:[446..447] -LRB-) (NN:[447..453] CYP1A1) (-RRB-:[453..454] -RRB-))) (VP (VBZ:[455..457] is) (VP (RP:[458..462] down) (HYPH:[462..463] -) (VBN:[463..472] regulated) (NP-1 (-NONE-:[472..472] *)) (PP-LOC (IN:[473..475] at) (NP (DT:[476..479] the) (JJ:[480..495] transcriptional) (NN:[496..501] level))) (PP (IN:[502..504] by) (NP-LGS (JJ:[505..514] oxidative) (NN:[515..521] stress)))))))) (.:[521..522] .))) ;sentence 7 Span:524..702 ;Basal as well as 2,3,7, 8-tetrachloro-p-dioxin-induced promoter activities ;are strongly impaired by H2O2 treatment or glutathione depletion with ;L-buthionine-(S,R)-sulfoximine. ;[541..570]:substance:"2,3,7, 8-tetrachloro-p-dioxin" ;[579..587]:substance:"promoter" ;[625..629]:substance:"H2O2" ;[643..654]:substance:"glutathione" ;[671..701]:substance:"L-buthionine-(S,R)-sulfoximine" (SENT (S (NP-SBJ-2 (NP (JJ:[524..529] Basal) (NML-1 (-NONE-:[529..529] *P*))) (CONJP (RB:[530..532] as) (RB:[533..537] well) (IN:[538..540] as)) (NP (ADJP (NN:[541..547] 2,3,7,) (NN:[548..570] 8-tetrachloro-p-dioxin) (HYPH:[570..571] -) (VBN:[571..578] induced)) (NML-1 (NN:[579..587] promoter) (NNS:[588..598] activities)))) (VP (VBP:[599..602] are) (ADVP-MNR (RB:[604..612] strongly)) (VP (VBN:[613..621] impaired) (NP-2 (-NONE-:[621..621] *)) (PP (IN:[622..624] by) (NP-LGS (NP (NN:[625..629] H2O2) (NN:[630..639] treatment)) (CC:[640..642] or) (NP (NP (NN:[643..654] glutathione) (NN:[655..664] depletion)) (PP (IN:[665..669] with) (NP (NN:[671..701] L-buthionine--LRB-S,R-RRB--sulfoximine)))))))) (.:[701..702] .))) ;sentence 8 Span:703..841 ;Tumor necrosis factor alpha inhibits CYP1A1 expression, and this inhibition ;is prevented by the antioxidant pyrrolidine dithiocarbamate. ;[703..730]:substance:"Tumor necrosis factor alpha" ;[740..746]:cyp450:"CYP1A1" ;[800..811]:substance:"antioxidant" ;[812..840]:substance:"pyrrolidine dithiocarbamate" (SENT (S (S (NP-SBJ (NN:[703..708] Tumor) (NN:[709..717] necrosis) (NN:[718..724] factor) (SYM:[725..730] alpha)) (VP (VBZ:[731..739] inhibits) (NP (NN:[740..746] CYP1A1) (NN:[748..758] expression)))) (,:[758..759] ,) (CC:[760..763] and) (S (NP-SBJ-1 (DT:[764..768] this) (NN:[769..779] inhibition)) (VP (VBZ:[780..782] is) (VP (VBN:[783..792] prevented) (NP-1 (-NONE-:[792..792] *)) (PP (IN:[793..795] by) (NP-LGS (NP (DT:[796..799] the) (JJ:[800..811] antioxidant)) (NP (NN:[812..823] pyrrolidine) (NN:[825..840] dithiocarbamate))))))) (.:[840..841] .))) ;sentence 9 Span:842..966 ;We show that these regulations depend on the integrity of the nuclear factor ;1 (NFI) site located in the proximal promoter. ;[923..926]:substance:"NFI" ;[957..965]:substance:"promoter" (SENT (S (NP-SBJ (PRP:[842..844] We)) (VP (VBP:[845..849] show) (SBAR (IN:[850..854] that) (S (NP-SBJ (DT:[855..860] these) (NNS:[861..872] regulations)) (VP (VBP:[873..879] depend) (PP-CLR (IN:[880..882] on) (NP (NP (DT:[883..886] the) (NN:[887..896] integrity)) (PP (IN:[897..899] of) (NP (NP (NML (NML (DT:[900..903] the) (JJ:[905..912] nuclear) (NN:[913..919] factor) (CD:[920..921] 1)) (NML (-LRB-:[922..923] -LRB-) (NN:[923..926] NFI) (-RRB-:[926..927] -RRB-))) (NN:[928..932] site)) (VP (VBN:[933..940] located) (NP (-NONE-:[940..940] *)) (PP-LOC (IN:[941..943] in) (NP (DT:[944..947] the) (JJ:[948..956] proximal) (NN:[957..965] promoter)))))))))))) (.:[965..966] .))) ;sentence 10 Span:967..1040 ;We therefore examined the redox regulation of this transcription factor. ;[1019..1039]:substance:"transcription factor" (SENT (S (NP-SBJ (PRP:[967..969] We)) (ADVP (RB:[970..979] therefore)) (VP (VBD:[981..989] examined) (NP (NP (DT:[990..993] the) (NN:[994..999] redox) (NN:[1000..1010] regulation)) (PP (IN:[1011..1013] of) (NP (DT:[1014..1018] this) (NN:[1019..1032] transcription) (NN:[1033..1039] factor))))) (.:[1039..1040] .))) ;sentence 11 Span:1041..1225 ;Treatment of human HepG2 or rat H4 hepatoma cells with H2O2 or ;L-buthionine-(S, R)-sulfoximine inactivates the binding of the NFI ;transcription factor to its DNA consensus sequence. ;[1097..1101]:substance:"H2O2" ;[1105..1136]:substance:"L-buthionine-(S, R)-sulfoximine" ;[1169..1193]:substance:"NFI transcription factor" ;[1201..1204]:substance:"DNA" (SENT (S (NP-SBJ (NP (NN:[1041..1050] Treatment)) (PP (IN:[1051..1053] of) (NP (NP (JJ:[1054..1059] human) (NN:[1061..1066] HepG2)) (CC:[1067..1069] or) (NP (NN:[1070..1073] rat) (NN:[1074..1076] H4) (NN:[1077..1085] hepatoma) (NNS:[1086..1091] cells)))) (PP (IN:[1092..1096] with) (NP (NP (NN:[1097..1101] H2O2)) (CC:[1102..1104] or) (NP (NN:[1105..1121] L-buthionine--LRB-S,) (NN:[1122..1136] R-RRB--sulfoximine))))) (VP (VBZ:[1138..1149] inactivates) (NP (NP (DT:[1150..1153] the) (NN:[1154..1161] binding)) (PP (IN:[1162..1164] of) (NP (DT:[1165..1168] the) (NN:[1169..1172] NFI) (NN:[1173..1186] transcription) (NN:[1187..1193] factor))) (PP (TO:[1194..1196] to) (NP (PRP$:[1197..1200] its) (NN:[1201..1204] DNA) (NN:[1205..1214] consensus) (NN:[1216..1224] sequence))))) (.:[1224..1225] .))) ;sentence 12 Span:1226..1368 ;Furthermore, H2O2 treatment leads to a dose-dependent decrease of reporter ;gene expressions driven by promoters containing NFI binding sites. ;[1239..1243]:substance:"H2O2" ;[1329..1338]:substance:"promoters" ;[1350..1353]:substance:"NFI" (SENT (S (ADVP (RB:[1226..1237] Furthermore)) (,:[1237..1238] ,) (NP-SBJ (NN:[1239..1243] H2O2) (NN:[1244..1253] treatment)) (VP (VBZ:[1254..1259] leads) (PP-CLR (TO:[1260..1262] to) (NP (NP (DT:[1263..1264] a) (ADJP (NN:[1265..1269] dose) (HYPH:[1269..1270] -) (JJ:[1270..1279] dependent)) (NN:[1280..1288] decrease)) (PP (IN:[1289..1291] of) (NP (NP (NML (NN:[1293..1301] reporter) (NN:[1302..1306] gene)) (NNS:[1307..1318] expressions)) (VP (VBN:[1319..1325] driven) (NP (-NONE-:[1325..1325] *)) (PP (IN:[1326..1328] by) (NP-LGS (NP (NNS:[1329..1338] promoters)) (VP (VBG:[1339..1349] containing) (NP (NN:[1350..1353] NFI) (NN:[1354..1361] binding) (NNS:[1362..1367] sites))))))))))) (.:[1367..1368] .))) ;sentence 13 Span:1370..1452 ;Glutathione depletion and catalase inhibition also repress a NFI-driven ;promoter. ;[1370..1381]:substance:"Glutathione" ;[1396..1404]:substance:"catalase" ;[1431..1434]:substance:"NFI" ;[1443..1451]:substance:"promoter" (SENT (S (NP-SBJ (NP (NN:[1370..1381] Glutathione) (NN:[1382..1391] depletion)) (CC:[1392..1395] and) (NP (NN:[1396..1404] catalase) (NN:[1405..1415] inhibition))) (ADVP (RB:[1416..1420] also)) (VP (VBP:[1421..1428] repress) (NP (DT:[1429..1430] a) (ADJP (NN:[1431..1434] NFI) (HYPH:[1434..1435] -) (VBN:[1435..1441] driven)) (NN:[1443..1451] promoter))) (.:[1451..1452] .))) ;sentence 14 Span:1453..1556 ;Under the same conditions, the CP-1 transcription factor activity is not ;affected by oxidative stress. ;[1484..1509]:substance:"CP-1 transcription factor" (SENT (S (PP (IN:[1453..1458] Under) (NP (DT:[1459..1462] the) (JJ:[1463..1467] same) (NNS:[1468..1478] conditions))) (,:[1478..1479] ,) (NP-SBJ-2 (DT:[1480..1483] the) (NML (NN:[1484..1488] CP-1) (NN:[1489..1502] transcription) (NN:[1503..1509] factor)) (NN:[1510..1518] activity)) (VP (VBZ:[1519..1521] is) (RB:[1523..1526] not) (VP (VBN:[1527..1535] affected) (NP-2 (-NONE-:[1535..1535] *)) (PP (IN:[1536..1538] by) (NP-LGS (JJ:[1539..1548] oxidative) (NN:[1549..1555] stress))))) (.:[1555..1556] .))) ;sentence 15 Span:1557..1617 ;Thus, NFI seems particularly sensitive to oxidative stress. ;[1563..1566]:substance:"NFI" (SENT (S (ADVP (RB:[1557..1561] Thus)) (,:[1561..1562] ,) (NP-SBJ (NN:[1563..1566] NFI)) (VP (VBZ:[1567..1572] seems) (ADJP-PRD (RB:[1573..1585] particularly) (JJ:[1586..1595] sensitive) (PP (TO:[1596..1598] to) (NP (JJ:[1600..1609] oxidative) (NN:[1610..1616] stress))))) (.:[1616..1617] .))) ;sentence 16 Span:1618..1699 ;This accounts, at least partially, for the regulation of cyp1A1 gene ;expression. ;[1676..1682]:cyp450:"cyp1A1" (SENT (S (NP-SBJ (DT:[1618..1622] This)) (VP (VBZ:[1623..1631] accounts) (,:[1631..1632] ,) (ADVP (IN:[1633..1635] at) (RBS:[1636..1641] least) (RB:[1642..1651] partially)) (,:[1651..1652] ,) (PP-CLR (IN:[1653..1656] for) (NP (NP (DT:[1657..1660] the) (NN:[1661..1671] regulation)) (PP (IN:[1672..1674] of) (NP (NN:[1676..1682] cyp1A1) (NN:[1683..1687] gene) (NN:[1688..1698] expression)))))) (.:[1698..1699] .))) ;section 17 Span:1703..1747 ;PMID: 9756946 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1703..1707] PMID) (::[1707..1708] :) (CD:[1709..1716] 9756946) (NN:[1717..1718] -LSB-) (NNP:[1718..1724] PubMed) (::[1725..1726] -) (NN:[1727..1734] indexed) (IN:[1735..1738] for) (NNP:[1739..1747] MEDLINE-RSB-)))