????????PYDDT??Keap1-Nrf2??????? - PowerPoint PPT Presentation

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????????PYDDT??Keap1-Nrf2???????

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PYDDT Keap1-Nrf2 , Email: zhangxy_zju_at_hotmail.com – PowerPoint PPT presentation

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Title: ????????PYDDT??Keap1-Nrf2???????


1
????????PYDDT??Keap1-Nrf2???????
??????? ???, ??? ?????? Email
zhangxy_zju_at_hotmail.com
-1-
2
????
???????????????????,??????????????????????????????
???????????????NAD(P)H ??????(NQO1)?????(OH-1)???
??????(GST)??
????????????????????,????????1040???????????????
???(2004-2010)??????????????,????????????????
?????????????????????????????????????????????????
??????,?????????????,?????????????????????????????
??
?????? (isothiocyanates)
???
????? (stilbenes)
??
-2-
3
????
???????????ARE?????,??????????????Nrf2????????????
?,????Nrf2?Keap1????????????Keap1-Cul3-Rbx????????
?????????????,Nrf2??Keap1???????????,??????????,??
ARE?????????????? PYDDT??????????????????????????
???????(2005??)??????????????????????
?1 Keap1-Nrf2?????
?2 PYDDT?????
-3-
4
?????
  • ??????IC50?
  • NQO1???????CD?
  • Western Blotting????????
  • LC-MSNMR????PYDDT?GSH????
  • ??????Nrf2???????????????
  • ??????Keap1?????????
  • DTNB??????GSH??
  • ??????????ROS??
  • ???????????????????????

-4-
5
????
1. PYDDT??????????????,?????????Keap1-Nrf2?????
?3 PYDDT??Keap1-Nrf2?????????????
-5-
6
????
2. PYDDT?????????GSH????,??????4??????????GSH??,??
?ROS??
?4 PYDDT??????GSH????
-6-
7
????
2. PYDDT?????????GSH????,??????4??????????GSH??,??
?ROS??
23
?5 PYDDT????????????GSH??,???ROS??
-7-
8
????
3. PYDDT??Nrf2?Nrf2???NQO1????????GSH??
?6 ???GSH?PYDDT??Keap1-Nrf2?????????????
-8-
9
????
4. PYDDT???????GSH/GSSG?????????????????????,?????
?Keap1
?8 PYDDT??????????????
?7 Thiol-disulfide exchange??
-9-
10
????
5. ?????????,?Keap1?Cys434?????????,Keap1?Nrf2????
?????
Keap1?GSSG???????,??LC-MS??,?????????????????? Che
m. Res. Toxicol. 2008, 21, 20512060.
?????
?9 Keap1?Cys434????????????Keap1-Nrf2??????
-10-
11
?????
1. PYDDY????????????????,???????????????????????,?
?PYDDT????????????????????????
?10 PYDDT??Keap1-Nrf2???????
?11 PYDDT?????????
-11-
12
?????
2. ?????????????(???????????????????)?????????????
????????????????????????????,?????????????????????
?????????????????????????????????????????????GSH?
?,??GSH????????????????(????????????),????????????
??
-12-
13
?????
???????? (Michael addition acceptors)
1???Keap1-Nrf2?? 2???NF-?B 3????? 4????????
??????
?????????????????????????
??????
1??????GSH????????? 2???????
-13-
14
??
???????????????????????????????!
-14-
15
Thank You !
-15-
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