Repression of oxidant-induced nuclear factor-kappaB activity mediates placental cytokine responses in gestational diabetes.
Repression of oxidant-induced nuclear factor-kappaB activity mediates placental cytokine responses in gestational diabetes.
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妊娠糖尿病中氧化剂诱导的核因子 kappaB 活性的抑制介导胎盘细胞因子反应。
DOI：
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发表时间：
2004
影响因子：
5.8
通讯作者：
G. Rice
中科院分区：
文献类型：
--
作者：
M. Coughlan;M. Permezel;H. Georgiou;G. Rice
虽然氧化应激与2型糖尿病的发病机制有关，但有关氧化应激在妊娠期糖尿病(GDM)中的作用的数据有限，GDM是一种类似的病理生理疾病。促炎症细胞因子TNFα、IL-6和IL-8在足月时从胎盘中释放出来，参与和/或与各种代谢事件有关，包括胰岛素敏感性降低。此前，我们报道了妊娠期糖尿病患者和非妊娠期糖尿病患者的胎盘和脂肪组织非原位释放促炎细胞因子的差异。我们认为，这些差异反映了GDM组织对氧化应激的预暴露和/或适应。在这项研究中，我们验证了GDM患者的胎盘组织比正常女性的胎盘组织对氧化应激反应更弱的假设。在基础状态下，对照组和GDM组的肿瘤坏死因子α、IL-6和IL-8的释放情况相似。然而，GDM组的8-异前列腺素释放量是GDM组的2倍(P<；0.01)。作为对氧化应激的响应，正常组织中肿瘤坏死因子α和8-异前列腺素的释放以及核因子-kappaB的DNA结合活性显著增加(分别是20倍、2倍和35%，P<；0.01)。相反，GDM组织对氧化应激的反应迟钝，8-异前列腺素的释放没有变化，TNFpha的释放增加了4倍，而NF-kappaB DNA结合活性降低了40%。这些数据支持这样的假设，即妊娠期糖尿病患者的胎盘显示出通过抑制核因子-kappaB活性而对氧化应激做出反应的能力降低。
Although oxidative stress has been implicated in the pathogenesis of type 2 diabetes, limited data are available regarding its role in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The proinflammatory cytokines TNFalpha, IL-6, and IL-8 are released from the placenta at term and have been implicated in and/or associated with various metabolic events, including decreased insulin sensitivity. Previously we reported differences in the ex situ release of proinflammatory cytokines from placental and adipose tissues obtained from women with and without GDM. We proposed that these differences reflect preexposure and/or adaptation to oxidative stress by GDM tissues. In this study, we tested the hypothesis that placental tissue from women with GDM is less responsive to oxidative stress than tissue from normal women. Under basal conditions, release of TNFalpha, IL-6, and IL-8 was similar in both control and GDM groups. However, 8-isoprostane release was 2-fold greater in the GDM group (P < 0.01). In response to oxidative stress, TNFalpha and 8-isoprostane release and nuclear factor-kappaB (NF-kappaB) DNA-binding activity were significantly increased in normal tissues (20-fold, 2-fold, and 35%, respectively, P < 0.01). In contrast, the response of GDM tissues to oxidant stress was blunted, with no change in 8-isoprostane release, a 4-fold increase in TNFalpha release, and a 40% reduction in NF-kappaB DNA-binding activity. These data support the hypothesis that placentae from women with GDM display a reduced capacity, mediated by repression of NF-kappaB activity, to respond to oxidative stress.
影响因子：
158.5
作者：
MORROW, JD;FREI, B;ROBERTS, LJ
通讯作者：
ROBERTS, LJ
影响因子：
4.8
作者：
A. Chawla;E. Schwarz;D. Dimaculangan;M. Lazar
通讯作者：
A. Chawla;E. Schwarz;D. Dimaculangan;M. Lazar
DOI：
10.1073/pnas.87.23.9383
发表时间：
1990-12-01
影响因子：
11.1
作者：
MORROW, JD;HILL, KE;ROBERTS, LJ
通讯作者：
ROBERTS, LJ