0 7 Effects Effect NNPS 8 10 of of IN 11 23 alpha-lipoic alpha-lipoic JJ 24 28 acid acid NN 29 32 and and CC 33 46 dihydrolipoic dihydrolipoic JJ 47 51 acid acid NN 52 54 on on IN 55 65 expression expression NN 66 68 of of IN 69 83 proto-oncogene proto-oncogene NN 84 89 c-fos c-fos NN 89 90 . . . 92 95 The the DT 96 109 transcription transcription NN 110 116 factor factor NN 117 121 AP-1 ap-1 NN 122 124 is be VBZ 125 127 an an DT 128 137 important important JJ 138 143 human human JJ 144 152 mediator mediator NN 153 155 of of IN 156 159 the the DT 160 168 cellular cellular JJ 169 177 response response NN 178 180 to to TO 181 186 serum serum NN 186 187 , , , 188 194 growth growth NN 195 202 factors factor NNS 202 203 , , , 204 207 and and CC 208 215 phorbol phorbol NN 216 222 esters ester NNS 223 227 such such JJ 228 230 as as IN 231 260 12-O-tetradecanoyl-phorbol-13 12-o-tetradecanoyl-phorbol-13 NN 261 268 acetate acetate NN 269 270 ( ( ( 270 273 TPA TPA NNP 273 274 ) ) ) 274 275 . . . 276 279 The the DT 280 284 AP-1 ap-1 NN 285 292 complex complex NN 293 301 consists consist VBZ 302 304 of of IN 305 313 distinct distinct JJ 314 321 protein protein NN 322 334 heterodimers heterodimer NNS 335 342 encoded encode VBN 343 345 by by IN 346 349 the the DT 350 364 proto-oncogene proto-oncogene NN 365 370 c-fos c-fos NN 371 374 and and CC 375 380 c-jun c-jun NN 381 385 mRNA mrna NN 386 391 whose whose WP$ 392 396 gene gene NN 397 407 expression expression NN 408 411 can can MD 412 414 be be VB 415 422 induced induce VBN 423 425 by by IN 426 429 TPA TPA NNP 429 430 , , , 431 437 cyclic cyclic JJ 438 441 AMP amp NN 442 445 and and CC 446 452 growth growth NN 453 460 factors factor NNS 460 461 . . . 462 468 Recent recent JJ 469 477 findings finding NNS 478 485 suggest suggest VBP 486 488 an an DT 489 500 involvement involvement NN 501 503 of of IN 504 512 reactive reactive JJ 513 519 oxygen oxygen NN 520 527 species specie NNS 528 530 in in IN 531 534 the the DT 535 542 pathway pathway NN 543 545 of of IN 546 549 TPA TPA NNP 550 553 and and CC 554 561 protein protein NN 562 568 kinase kinase NNP 569 570 C C NNP 571 578 leading lead VBG 579 581 to to TO 582 592 expression expression NN 593 595 of of IN 596 601 c-fos c-fos NN 602 605 and and CC 606 611 c-jun c-jun NN 612 616 mRNA mrna NN 616 617 . . . 618 620 To to TO 621 632 investigate investigate VB 633 636 the the DT 637 641 role role NN 642 644 of of IN 645 653 reactive reactive JJ 654 660 oxygen oxygen NN 661 668 species specie NNS 669 671 we we PRP 672 679 studied study VBD 680 683 the the DT 684 691 effects effect NNS 692 694 of of IN 695 707 alpha-lipoic alpha-lipoic JJ 708 712 acid acid NN 713 716 and and CC 717 730 dihydrolipoic dihydrolipoic JJ 731 735 acid acid NN 736 737 ( ( ( 737 744 natural natural JJ 745 750 thiol thiol NN 751 763 antioxidants antioxidant NNS 763 764 ) ) ) 765 767 on on IN 768 771 the the DT 772 782 expression expression NN 783 785 of of IN 786 791 c-fos c-fos NN 792 796 mRNA mrna NN 797 799 in in IN 800 805 human human JJ 806 812 Jurkat Jurkat NNP 813 814 T t NN 815 820 cells cell NNS 820 821 . . . 822 826 When when WRB 827 832 cells cell NNS 833 837 were be VBD 838 850 preincubated preincubate VBN 851 855 with with IN 856 869 dihydrolipoic dihydrolipoic JJ 870 874 acid acid NN 875 876 ( ( ( 876 879 0.2 0.2 CD 880 882 mM mM NNP 882 883 ) ) ) 884 887 the the DT 888 898 expression expression NN 899 901 of of IN 902 907 c-fos c-fos NN 908 912 mRNA mRNA NNP 913 916 was be VBD 917 927 suppressed suppress VBN 928 930 at at IN 931 933 30 30 CD 934 937 min min NN 938 943 after after IN 944 955 stimulation stimulation NN 956 958 of of IN 959 962 TPA TPA NNP 963 964 ( ( ( 964 967 0.5 0.5 CD 968 974 microM microM NNP 974 975 ) ) ) 976 983 whereas whereas IN 984 986 in in IN 987 990 the the DT 991 995 case case NN 996 998 of of IN 999 1012 preincubation preincubation NN 1013 1015 of of IN 1016 1028 alpha-lipoic alpha-lipoic JJ 1029 1033 acid acid NN 1034 1035 ( ( ( 1035 1038 0.2 0.2 CD 1039 1045 microM microM NNP 1045 1046 ) ) ) 1046 1047 , , , 1048 1051 the the DT 1052 1062 expression expression NN 1063 1066 was be VBD 1067 1075 enhanced enhance VBN 1076 1078 at at IN 1079 1081 30 30 CD 1082 1085 min min NN 1085 1086 . . . 1087 1092 These these DT 1093 1100 studies study NNS 1101 1108 support support VBP 1109 1112 the the DT 1113 1117 idea idea NN 1118 1122 that that IN 1123 1133 superoxide superoxide NN 1134 1139 anion anion NN 1140 1147 radical radical NN 1148 1153 plays play VBZ 1154 1155 a a DT 1156 1160 role role NN 1161 1163 in in IN 1164 1167 the the DT 1168 1178 expression expression NN 1179 1181 of of IN 1182 1187 c-fos c-fos NN 1188 1192 mRNA mrna NN 1192 1193 . . .