;PMID: 8781507 ;source_file_1919.mrg ;Release 0.9 of PennBioIE ;Funded by NSF ITR EIA-0205448 ;0)section:[e:0..43] = [t:0..43] ;1)sentence:[e:49..102] = [t:49..102] ;2)section:[e:106..152] = [t:106..152] ;3)section:[e:156..233] = [t:156..233] ;4)sentence:[e:237..387] = [t:237..387] ;5)sentence:[e:388..667] = [t:388..667] ;6)sentence:[e:668..756] = [t:668..756] ;7)sentence:[e:757..807] = [t:757..807] ;8)sentence:[e:808..1014] = [t:808..1014] ;9)sentence:[e:1015..1180] = [t:1015..1180] ;10)sentence:[e:1181..1345] = [t:1181..1345] ;11)sentence:[e:1346..1436] = [t:1346..1436] ;12)section:[e:1440..1484] = [t:1440..1484] ;section 0 Span:0..43 ;Biochem Pharmacol. 1996 Sep 27;52(6):885-9. (SEC (FRAG (NNP:[0..7] Biochem) (NNP:[8..17] Pharmacol) (.:[17..18] .) (``:[19..23] 1996) (NNP:[24..27] Sep) (CD:[28..34] 27;52-LRB-) (CD:[34..35] 6) (-RRB-:[35..36] -RRB-) (::[36..37] :) (CD:[37..39] 88) (CD:[39..40] 5) (HYPH:[40..41] -) (CD:[41..43] 9.))) ;sentence 1 Span:49..102 ;Interaction of nonylphenol and hepatic CYP1A in rats. ;[64..75]:substance:"nonylphenol" ;[88..93]:cyp450:"CYP1A" (SENT (NP-HLN (NP (NN:[49..60] Interaction)) (PP (IN:[61..63] of) (NP (NP (NN:[64..75] nonylphenol)) (CC:[76..79] and) (NP (JJ:[80..87] hepatic) (NN:[88..93] CYP1A)))) (PP-LOC (IN:[94..96] in) (NP (NNS:[97..101] rats))) (.:[101..102] .))) ;section 2 Span:106..152 ;Lee PC, Patra SC, Stelloh CT, Lee W, Struve M. (SEC (FRAG (NNP:[106..109] Lee) (NNP:[110..112] PC) (,:[112..113] ,) (NNP:[114..119] Patra) (NNP:[120..122] SC) (,:[122..123] ,) (NNP:[124..131] Stelloh) (NNP:[132..134] CT) (,:[134..135] ,) (NNP:[136..139] Lee) (NNP:[140..141] W) (,:[141..142] ,) (NNP:[143..149] Struve) (NNP:[150..152] M.))) ;section 3 Span:156..233 ;Department of Pediatrics, Medical College of Wisconsin, Milwaukee 53226, ;USA. (SEC (FRAG (NNP:[156..166] Department) (IN:[167..169] of) (NNP:[170..180] Pediatrics) (,:[180..181] ,) (NNP:[182..189] Medical) (NNP:[190..197] College) (IN:[198..200] of) (NNP:[201..210] Wisconsin) (,:[210..211] ,) (NNP:[212..221] Milwaukee) (CD:[222..227] 53226) (,:[227..228] ,) (NNP:[229..232] USA) (.:[232..233] .))) ;sentence 4 Span:237..387 ;Both estradiol and nonylphenol (NP) inhibited hepatic microsomal ;7-ethoxyresorufin O-deethylase (EROD) activity of beta-naphthoflavone-treated ; rats. ;[242..251]:substance:"estradiol" ;[256..267]:substance:"nonylphenol" ;[269..271]:substance:"NP" ;[303..333]:cyp450:"7-ethoxyresorufin O-deethylase" ;[335..339]:cyp450:"EROD" ;[353..372]:substance:"beta-naphthoflavone" (SENT (S (NP-SBJ (CC:[237..241] Both) (NP (NN:[242..251] estradiol)) (CC:[252..255] and) (NP (NP (NN:[256..267] nonylphenol)) (NP (-LRB-:[268..269] -LRB-) (NN:[269..271] NP) (-RRB-:[271..272] -RRB-)))) (VP (VBD:[273..282] inhibited) (NP (NP (NML (JJ:[283..290] hepatic) (JJ:[291..301] microsomal) (NML (NML (NN:[303..320] 7-ethoxyresorufin) (NN:[321..333] O-deethylase)) (NML (-LRB-:[334..335] -LRB-) (NN:[335..339] EROD) (-RRB-:[339..340] -RRB-)))) (NN:[341..349] activity)) (PP (IN:[350..352] of) (NP (ADJP (NN:[353..372] beta-naphthoflavone) (HYPH:[372..373] -) (VBN:[373..380] treated)) (NNS:[382..386] rats))))) (.:[386..387] .))) ;sentence 5 Span:388..667 ;Enzyme kinetic analyses (Lineweaver-Burk plots) using different estradiol ;and NP concentrations with graded increases in the concentrations of the ;substrate, ethoxyresorufin, showed that the inhibition was of a competitive ;nature at all concentrations of estradiol or NP used. ;[388..394]:substance:"Enzyme" ;[452..461]:substance:"estradiol" ;[467..469]:substance:"NP" ;[537..546]:substance:"substrate" ;[548..563]:substance:"ethoxyresorufin" ;[646..655]:substance:"estradiol" ;[659..661]:substance:"NP" (SENT (S (NP-SBJ (NP (NP (NN:[388..394] Enzyme) (JJ:[395..402] kinetic) (NNS:[403..411] analyses)) (PRN (-LRB-:[412..413] -LRB-) (NP (NML (NNP:[413..423] Lineweaver) (HYPH:[423..424] -) (NNP:[424..428] Burk)) (NNS:[429..434] plots)) (-RRB-:[434..435] -RRB-))) (VP (VBG:[436..441] using) (NP (JJ:[442..451] different) (NML (NML (NN:[452..461] estradiol) (NML-1 (-NONE-:[461..461] *P*))) (CC:[463..466] and) (NML (NN:[467..469] NP) (NML-1 (NNS:[470..484] concentrations))))) (PP (IN:[485..489] with) (NP (NP (VBN:[490..496] graded) (NNS:[497..506] increases)) (PP (IN:[507..509] in) (NP (NP (DT:[510..513] the) (NNS:[514..528] concentrations)) (PP (IN:[529..531] of) (NP (NP (DT:[532..535] the) (NN:[537..546] substrate)) (,:[546..547] ,) (NP (NN:[548..563] ethoxyresorufin)))))))))) (,:[563..564] ,) (VP (VBD:[565..571] showed) (SBAR (IN:[572..576] that) (S (NP-SBJ (DT:[577..580] the) (NN:[581..591] inhibition)) (VP (VBD:[592..595] was) (PP-PRD (IN:[596..598] of) (NP (DT:[599..600] a) (JJ:[601..612] competitive) (NN:[614..620] nature))) (PP (IN:[621..623] at) (NP (NP (DT:[624..627] all) (NNS:[628..642] concentrations)) (PP (IN:[643..645] of) (NP (NP (NN:[646..655] estradiol) (CC:[656..658] or) (NN:[659..661] NP)) (VP (VBN:[662..666] used) (NP (-NONE-:[666..666] *))))))))))) (.:[666..667] .))) ;sentence 6 Span:668..756 ;Thus, the mechanism by which NP inhibits EROD activity is similar to that of ;estradiol. ;[698..700]:substance:"NP" ;[710..714]:cyp450:"EROD" ;[746..755]:substance:"estradiol" (SENT (S (RB:[668..672] Thus) (,:[672..673] ,) (NP-SBJ (NP (DT:[674..677] the) (NN:[678..687] mechanism)) (SBAR (WHPP-1 (IN:[688..690] by) (WHNP (WDT:[692..697] which))) (S (NP-SBJ (NN:[698..700] NP)) (VP (VBZ:[701..709] inhibits) (NP (NN:[710..714] EROD) (NN:[715..723] activity)) (PP-1 (-NONE-:[723..723] *T*)))))) (VP (VBZ:[724..726] is) (ADJP-PRD (JJ:[727..734] similar) (PP (TO:[735..737] to) (NP (NP (DT:[738..742] that)) (PP (IN:[743..745] of) (NP (NN:[746..755] estradiol))))))) (.:[755..756] .))) ;sentence 7 Span:757..807 ;NP, however, was much less potent than estradiol. ;[757..759]:substance:"NP" ;[797..806]:substance:"estradiol" (SENT (S (NP-SBJ (NN:[757..759] NP)) (,:[759..760] ,) (ADVP (RB:[761..768] however)) (VP (,:[768..769] ,) (VBD:[771..774] was) (ADJP-PRD (ADJP (ADVP (RB:[775..779] much) (RBR:[780..784] less)) (JJ:[785..791] potent)) (PP (IN:[792..796] than) (NP (NN:[797..806] estradiol))))) (.:[806..807] .))) ;sentence 8 Span:808..1014 ;Young rats treated in vivo with 80 mg/kg body weight of NP demonstrated a ;slight but significant decrease in their hepatic microsomal EROD activity ;and CYP1A protein as measured by western blot analysis. ;[840..842]:quantitative-value:"80" ;[843..861]:quantitative-units:"mg/kg body weight" ;[865..867]:substance:"NP" ;[944..948]:cyp450:"EROD" ;[962..975]:cyp450:"CYP1A protein" (SENT (S (NP-SBJ (NP (JJ:[808..813] Young) (NNS:[814..818] rats)) (VP (VBN:[819..826] treated) (NP (-NONE-:[826..826] *)) (ADVP (FW:[827..829] in) (FW:[830..834] vivo)) (PP (IN:[835..839] with) (NP (NP (CD:[840..842] 80) (NN:[843..845] mg)) (PP (SYM:[845..846] /) (NP (NP (NN:[846..848] kg)) (NP (NN:[850..854] body) (NN:[855..861] weight)))) (PP (IN:[862..864] of) (NP (NN:[865..867] NP))))))) (VP (VBD:[868..880] demonstrated) (NP (NP (DT:[881..882] a) (ADJP (JJ:[883..889] slight) (CC:[890..893] but) (JJ:[894..905] significant)) (NN:[906..914] decrease)) (PP-LOC (IN:[915..917] in) (NP (PRP$:[918..923] their) (NML (NML (NML (JJ:[925..932] hepatic) (JJ:[933..943] microsomal) (NN:[944..948] EROD)) (NN:[949..957] activity)) (CC:[958..961] and) (NML (NN:[962..967] CYP1A) (NN:[968..975] protein)))))) (SBAR (IN:[976..978] as) (S (NP-SBJ-1 (-NONE-:[978..978] *)) (VP (VBN:[979..987] measured) (NP-1 (-NONE-:[987..987] *)) (PP-MNR (IN:[988..990] by) (NP (NML (JJ:[991..998] western) (NN:[999..1003] blot)) (NN:[1005..1013] analysis))))))) (.:[1013..1014] .))) ;sentence 9 Span:1015..1180 ;In addition, treatment with NP led to a decrease in the steady-state levels ;of hepatic CYP1A mRNA in rats, suggesting that NP acted at the ;pre-translational level. ;[1043..1045]:substance:"NP" ;[1103..1113]:substance:"CYP1A mRNA" ;[1139..1141]:substance:"NP" (SENT (S (PP (IN:[1015..1017] In) (NP (NN:[1018..1026] addition))) (,:[1026..1027] ,) (NP-SBJ (NP (NN:[1028..1037] treatment)) (PP (IN:[1038..1042] with) (NP (NN:[1043..1045] NP)))) (VP (VBD:[1046..1049] led) (PP-CLR (TO:[1050..1052] to) (NP (NP (DT:[1053..1054] a) (NN:[1055..1063] decrease)) (PP (IN:[1064..1066] in) (NP (NP (DT:[1067..1070] the) (NML (JJ:[1071..1077] steady) (HYPH:[1077..1078] -) (NN:[1078..1083] state)) (NNS:[1085..1091] levels)) (PP (IN:[1092..1094] of) (NP (JJ:[1095..1102] hepatic) (NN:[1103..1108] CYP1A) (NN:[1109..1113] mRNA))))) (PP-LOC (IN:[1114..1116] in) (NP (NNS:[1117..1121] rats))))) (,:[1121..1122] ,) (S-ADV (NP-SBJ (-NONE-:[1122..1122] *)) (VP (VBG:[1123..1133] suggesting) (SBAR (IN:[1134..1138] that) (S (NP-SBJ (NN:[1139..1141] NP)) (VP (VBD:[1142..1147] acted) (PP (IN:[1148..1150] at) (NP (DT:[1151..1154] the) (ADJP (AFX:[1156..1159] pre) (HYPH:[1159..1160] -) (JJ:[1160..1173] translational)) (NN:[1174..1179] level))))))))) (.:[1179..1180] .))) ;sentence 10 Span:1181..1345 ;The competitive nature of inhibition by NP on hepatic microsomal EROD ;activity indirectly suggests that this compound is a possible substrate of ;the CYP1A enzyme. ;[1221..1223]:substance:"NP" ;[1247..1251]:cyp450:"EROD" ;[1291..1299]:substance:"compound" ;[1315..1324]:substance:"substrate" ;[1332..1344]:cyp450:"CYP1A enzyme" (SENT (S (NP-SBJ (NP (DT:[1181..1184] The) (JJ:[1185..1196] competitive) (NN:[1197..1203] nature)) (PP (IN:[1204..1206] of) (NP (NP (NN:[1207..1217] inhibition)) (PP (IN:[1218..1220] by) (NP (NN:[1221..1223] NP))))) (PP (IN:[1224..1226] on) (NP (NML (JJ:[1227..1234] hepatic) (JJ:[1236..1246] microsomal) (NN:[1247..1251] EROD)) (NN:[1252..1260] activity)))) (ADVP (RB:[1261..1271] indirectly)) (VP (VBZ:[1272..1280] suggests) (SBAR (IN:[1281..1285] that) (S (NP-SBJ (DT:[1286..1290] this) (NN:[1291..1299] compound)) (VP (VBZ:[1300..1302] is) (NP-PRD (NP (DT:[1303..1304] a) (JJ:[1305..1313] possible) (NN:[1315..1324] substrate)) (PP (IN:[1325..1327] of) (NP (DT:[1328..1331] the) (NN:[1332..1337] CYP1A) (NN:[1338..1344] enzyme)))))))) (.:[1344..1345] .))) ;sentence 11 Span:1346..1436 ;Furthermore, NP had a moderate modulating effect on the expression of CYP1A ;in rat liver. ;[1359..1361]:substance:"NP" ;[1417..1422]:cyp450:"CYP1A" (SENT (S (ADVP (RB:[1346..1357] Furthermore)) (,:[1357..1358] ,) (NP-SBJ (NN:[1359..1361] NP)) (VP (VBD:[1362..1365] had) (NP (NP (DT:[1366..1367] a) (JJ:[1368..1376] moderate) (VBG:[1377..1387] modulating) (NN:[1388..1394] effect)) (PP (IN:[1396..1398] on) (NP (NP (DT:[1399..1402] the) (NN:[1403..1413] expression)) (PP (IN:[1414..1416] of) (NP (NN:[1417..1422] CYP1A)))))) (PP-LOC (IN:[1423..1425] in) (NP (NN:[1426..1429] rat) (NN:[1430..1435] liver)))) (.:[1435..1436] .))) ;section 12 Span:1440..1484 ;PMID: 8781507 [PubMed - indexed for MEDLINE] (SEC (FRAG (NNP:[1440..1444] PMID) (::[1444..1445] :) (CD:[1446..1453] 8781507) (-LRB-:[1454..1455] -LSB-) (NNP:[1455..1461] PubMed) (HYPH:[1462..1463] -) (NN:[1464..1471] indexed) (IN:[1472..1475] for) (NNP:[1476..1483] MEDLINE) (-RRB-:[1483..1484] -RSB-)))