0 5 HIV-1 HIV-1 NNP 6 9 Tat Tat NNP 10 21 potentiates potentiate VBZ 22 33 TNF-induced tnf-induced JJ 34 42 NF-kappa NF-kappa NNP 43 44 B B NNP 45 55 activation activation NN 56 59 and and CC 60 72 cytotoxicity cytotoxicity NN 73 75 by by IN 76 84 altering alter VBG 85 88 the the DT 89 97 cellular cellular JJ 98 103 redox redox NN 104 109 state state NN 109 110 . . . 112 116 This this DT 117 122 study study NN 123 135 demonstrates demonstrate VBZ 136 140 that that IN 141 146 human human JJ 147 163 immunodeficiency immunodeficiency NN 164 169 virus virus NN 170 174 type type NN 175 176 1 1 CD 177 178 ( ( ( 178 183 HIV-1 HIV-1 NNP 183 184 ) ) ) 185 188 Tat Tat NNP 189 196 protein protein NN 197 206 amplifies amplify VBZ 207 210 the the DT 211 219 activity activity NN 220 222 of of IN 223 228 tumor tumor NN 229 237 necrosis necrosis NN 238 244 factor factor NN 245 246 ( ( ( 246 249 TNF TNF NNP 249 250 ) ) ) 250 251 , , , 252 253 a a DT 254 262 cytokine cytokine NN 263 267 that that WDT 268 278 stimulates stimulate VBZ 279 284 HIV-1 HIV-1 NNP 285 296 replication replication NN 297 304 through through IN 305 315 activation activation NN 316 318 of of IN 319 327 NF-kappa NF-kappa NNP 328 330 B. B. NNP 331 333 In in IN 334 338 HeLa HeLa NNP 339 344 cells cell NNS 345 351 stably stably RB 352 363 transfected transfecte VBN 364 368 with with IN 369 372 the the DT 373 378 HIV-1 HIV-1 NNP 379 382 tat tat NN 383 387 gene gene NN 388 389 ( ( ( 389 397 HeLa-tat hela-tat JJ 398 403 cells cell NNS 403 404 ) ) ) 404 405 , , , 406 416 expression expression NN 417 419 of of IN 420 423 the the DT 424 427 Tat Tat NNP 428 435 protein protein NN 436 444 enhanced enhance VBD 445 449 both both CC 450 461 TNF-induced tnf-induced JJ 462 472 activation activation NN 473 475 of of IN 476 484 NF-kappa NF-kappa NNP 485 486 B B NNP 487 490 and and CC 491 503 TNF-mediated tnf-mediated JJ 504 516 cytotoxicity cytotoxicity NN 516 517 . . . 518 519 A a DT 520 527 similar similar JJ 528 540 potentiation potentiation NN 541 543 of of IN 544 547 TNF TNF NNP 548 555 effects effect NNS 556 559 was be VBD 560 568 observed observe VBN 569 571 in in IN 572 578 Jurkat Jurkat NNP 579 580 T t NN 581 586 cells cell NNS 587 590 and and CC 591 595 HeLa HeLa NNP 596 601 cells cell NNS 602 609 treated treat VBN 610 614 with with IN 615 622 soluble soluble JJ 623 626 Tat Tat NNP 627 634 protein protein NN 634 635 . . . 636 648 TNF-mediated tnf-mediated JJ 649 659 activation activation NN 660 662 of of IN 663 671 NF-kappa NF-kappa NNP 672 673 B B NNP 674 677 and and CC 678 690 cytotoxicity cytotoxicity NN 691 699 involves involve VBZ 700 703 the the DT 704 717 intracellular intracellular JJ 718 727 formation formation NN 728 730 of of IN 731 739 reactive reactive JJ 740 746 oxygen oxygen NN 747 760 intermediates intermediate NNS 760 761 . . . 762 771 Therefore therefore RB 771 772 , , , 773 785 Tat-mediated tat-mediated JJ 786 793 effects effect NNS 794 796 on on IN 797 800 the the DT 801 809 cellular cellular JJ 810 815 redox redox NN 816 821 state state NN 822 826 were be VBD 827 835 analyzed analyze VBN 835 836 . . . 837 839 In in IN 840 844 both both CC 845 846 T t NN 847 852 cells cell NNS 853 856 and and CC 857 861 HeLa HeLa NNP 862 867 cells cell NNS 868 873 HIV-1 HIV-1 NNP 874 877 Tat Tat NNP 878 888 suppressed suppress VBD 889 892 the the DT 893 903 expression expression NN 904 906 of of IN 907 919 Mn-dependent mn-dependent JJ 920 930 superoxide superoxide NN 931 940 dismutase dismutase NN 941 942 ( ( ( 942 948 Mn-SOD Mn-SOD NNP 948 949 ) ) ) 949 950 , , , 951 952 a a DT 953 966 mitochondrial mitochondrial JJ 967 973 enzyme enzyme NN 974 978 that that WDT 979 981 is be VBZ 982 986 part part NN 987 989 of of IN 990 993 the the DT 994 1002 cellular cellular JJ 1003 1010 defense defense NN 1011 1017 system system NN 1018 1025 against against IN 1026 1035 oxidative oxidative JJ 1036 1042 stress stress NN 1042 1043 . . . 1044 1048 Thus thus RB 1048 1049 , , , 1050 1056 Mn-SOD Mn-SOD NNP 1057 1060 RNA RNA NNP 1061 1068 protein protein NN 1069 1075 levels level NNS 1076 1079 and and CC 1080 1088 activity activity NN 1089 1093 were be VBD 1094 1102 markedly markedly RB 1103 1110 reduced reduce VBN 1111 1113 in in IN 1114 1117 the the DT 1118 1126 presence presence NN 1127 1129 of of IN 1130 1133 Tat Tat NNP 1133 1134 . . . 1135 1144 Decreased decrease VBN 1145 1151 Mn-SOD Mn-SOD NNP 1152 1162 expression expression NN 1163 1166 was be VBD 1167 1177 associated associate VBN 1178 1182 with with IN 1183 1192 decreased decrease VBN 1193 1199 levels level NNS 1200 1202 of of IN 1203 1214 glutathione glutathione NN 1215 1218 and and CC 1219 1220 a a DT 1221 1226 lower low JJR 1227 1232 ratio ratio NN 1233 1235 of of IN 1236 1252 reduced:oxidized reduced:oxidized JJ 1253 1264 glutathione glutathione NN 1264 1265 . . . 1266 1267 A a DT 1268 1277 truncated truncate VBN 1278 1281 Tat Tat NNP 1282 1289 protein protein NN 1290 1291 ( ( ( 1291 1298 Tat1-72 tat1-72 NN 1298 1299 ) ) ) 1299 1300 , , , 1301 1306 known know VBN 1307 1309 to to TO 1310 1323 transactivate transactivate VB 1324 1327 the the DT 1328 1333 HIV-1 HIV-1 NNP 1334 1338 long long JJ 1339 1347 terminal terminal JJ 1348 1354 repeat repeat NN 1355 1356 ( ( ( 1356 1359 LTR LTR NNP 1359 1360 ) ) ) 1360 1361 , , , 1362 1364 no no RB 1365 1371 longer longer RBR 1372 1380 affected affect VBD 1381 1387 Mn-SOD mn-sod NN 1388 1398 expression expression NN 1398 1399 , , , 1400 1403 the the DT 1404 1412 cellular cellular JJ 1413 1418 redox redox NN 1419 1424 state state NN 1425 1427 or or CC 1428 1440 TNF-mediated tnf-mediated JJ 1441 1453 cytotoxicity cytotoxicity NN 1453 1454 . . . 1455 1459 Thus thus RB 1459 1460 , , , 1461 1464 our our PRP$ 1465 1476 experiments experiment NNS 1477 1488 demonstrate demonstrate VBP 1489 1493 that that IN 1494 1497 the the DT 1498 1508 C-terminal c-terminal JJ 1509 1515 region region NN 1516 1518 of of IN 1519 1524 HIV-1 HIV-1 NNP 1525 1528 Tat Tat NNP 1529 1531 is be VBZ 1532 1540 required require VBN 1541 1543 to to TO 1544 1552 suppress suppress VB 1553 1559 Mn-SOD mn-sod NN 1560 1570 expression expression NN 1571 1574 and and CC 1575 1577 to to TO 1578 1584 induce induce VB 1585 1598 pro-oxidative pro-oxidative JJ 1599 1609 conditions condition NNS 1610 1619 reflected reflect VBN 1620 1622 by by IN 1623 1624 a a DT 1625 1629 drop drop NN 1630 1632 in in IN 1633 1640 reduced reduce VBN 1641 1652 glutathione glutathione NN 1653 1654 ( ( ( 1654 1657 GSH GSH NNP 1657 1658 ) ) ) 1659 1662 and and CC 1663 1666 the the DT 1667 1679 GSH:oxidized gsh:oxidize VBN 1680 1683 GSH GSH NNP 1684 1685 ( ( ( 1685 1689 GSSG GSSG NNP 1689 1690 ) ) ) 1691 1697 ratio. ratio. NN 1698 1699 ( ( ( 1699 1707 ABSTRACT ABSTRACT NNP 1708 1717 TRUNCATED truncated VBN 1718 1720 AT at IN 1721 1724 250 250 CD 1725 1730 WORDS words NNS 1730 1731 ) ) )