Oxidative stress modulates PPAR gamma in vascular endothelial cells.
Oxidative stress modulates PPAR gamma in vascular endothelial cells.
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DOI：
10.1016/j.freeradbiomed.2010.03.007
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发表时间：
2010-06-15
影响因子：
7.4
通讯作者：
Hart, C. Michael
中科院分区：
文献类型：
--
作者：
Blanquicett, Carmelo;Kang, Bum-Yong;Ritzenthaler, Jeffrey D.;Jones, Dean P.;Hart, C. Michael
过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma，PPARγ）在血管调节中起重要作用。然而，氧化应激对PPARγ表达和活性的影响尚未明确。将人脐静脉内皮细胞（HUVECs）暴露于分级浓度的H2 O2中0.5-72 h，或将牛主动脉内皮细胞（BAECs）暴露于半胱氨酸（Cys）/胱氨酸（CySS）对的细胞外巯基/二硫键氧化还原电位（Eh）的改变。在2 h内，H2 O2降低HUVEC的PPARγ mRNA和活性，并降低两个PPARγ调节基因的表达，而不改变PPARγ蛋白水平。H2 O2暴露4 h后，mRNA水平仍下降，而PPARγ活性恢复至对照水平。H2 O2暴露后72 h，PPARγ mRNA水平仍保持较低水平，但活性无明显变化。过氧化氢酶阻止H2 O2诱导的PPARγ mRNA和活性的降低。H2 O2 1）降低了瞬时转染人PPARγ启动子报告基因的HUVEC中荧光素酶的表达，2）未能改变PPARγ mRNA的半衰期，3）瞬时增加了c-Fos和磷酸化c-Jun. AP-1抑制剂姜黄素的表达和活性，阻止了H2 O2介导的PPARγ表达的降低。此外，具有氧化Eh的培养基降低BAEC PPARγ mRNA和活性。这些发现表明，氧化应激可能通过激活抑制性氧化还原调节转录因子，通过抑制PPARγ转录来减弱血管内皮细胞中的PPARγ表达和活性。
The peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in vascular regulation. However, the impact of oxidative stress on PPARγ expression and activity has not been clearly defined. Human umbilical vein endothelial cells (HUVECs) were exposed to graded concentrations of H2O2 for 0.5–72 h, or bovine aortic endothelial cells (BAECs) were exposed to alterations in extracellular thiol/disulfide redox potential (Eh) of the cysteine (Cys)/cystine (CySS) couple. Within 2 h, H2O2 reduced HUVEC PPARγ mRNA and activity and reduced the expression of two PPARγ-regulated genes without altering PPARγ protein levels. After 4 h H2O2 exposure, mRNA levels remained reduced while PPARγ activity returned to control levels. PPARγ mRNA levels remained depressed for up to 72 h after exposure to H2O2, without any change in PPARγ activity. Catalase prevented H2O2-induced reductions in PPARγ mRNA and activity. H2O2 1) reduced luciferase expression in HUVECs transiently transfected with a human PPARγ promoter reporter, 2) failed to alter PPARγ mRNA half-life, and 3) transiently increased expression and activity of c-Fos and phospho-c-Jun. Treatment with the AP-1 inhibitor, curcumin, prevented H2O2-mediated reductions in PPARγ expression. In addition, media having an oxidized Eh reduced BAEC PPARγ mRNA and activity. These findings demonstrate that oxidative stress, potentially through activation of inhibitory redox-regulated transcription factors, attenuates PPARγ expression and activity in vascular endothelial cells through suppression of PPARγ transcription.
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影响因子：
56.9
作者：
HWANG, C;SINSKEY, AJ;LODISH, HF
通讯作者：
LODISH, HF
影响因子：
4.4
作者：
Jaramillo, M;Olivier, M
通讯作者：
Olivier, M
影响因子：
5.5
作者：
Hwang, JN;Kleinhenz, DJ;Hart, CM
通讯作者：
Hart, CM
DOI：
10.1046/j.1440-1681.1999.03082.x
发表时间：
1999-07-01
影响因子：
2.9
作者：
Itoh, H;Doi, K;Naka, K
通讯作者：
Naka, K
影响因子：
3.2
作者：
El Midaoui, A;Wu, LY;de Champlain, J
通讯作者：
de Champlain, J