Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: effects of antioxidant vitamins.
Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen-activated protein kinase signaling pathways regulate proinflammatory cytokines and apoptosis in human placental explants in response to oxidative stress: effects of antioxidant vitamins.
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核因子-kappa B、p38 和应激激活蛋白激酶丝裂原激活蛋白激酶信号通路调节人胎盘外植体中的促炎细胞因子和细胞凋亡，以响应氧化应激：抗氧化维生素的作用。
DOI：
10.2353/ajpath.2007.061035
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发表时间：
2007-05
影响因子：
6
通讯作者：
Burton, Graham J.
中科院分区：
文献类型：
--
作者：
Cindrova-Davies, Tereza;Spasic-Boskovic, Olivera;Jauniaux, Eric;Charnock-Jones, D. Stephen;Burton, Graham J.
先兆子痫是人类妊娠的一种潜在致命并发症，其特征为高血压、蛋白尿和水肿。胎盘氧化应激是该综合征发病机制的关键因素，会导致多种因子的释放，包括促炎细胞因子和凋亡碎片，进而导致母体内皮细胞激活。这种释放背后的中间分子机制尚不清楚，但它们代表了治疗干预的潜在目标。我们在体外检查了绒毛外植体缺氧-复氧过程中信号通路的激活。缺氧复氧激活了 p38 和应激激活蛋白激酶丝裂原激活蛋白激酶 (MAPK) 以及核因子-κB 通路。下游后果包括肿瘤坏死因子-α 和白介素-1β 的组织浓度和分泌增加、环氧合酶-2 表达增加以及细胞凋亡增加。给外植体施用维生素 C 和 E 可阻断 p38 和应激激活蛋白激酶 MAPK 以及核因子-κB 通路的激活。维生素给药或 p38 通路抑制也降低了环氧合酶 2 的表达、肿瘤坏死因子 α 和白细胞介素 1β 的分泌以及细胞凋亡的水平。我们得出的结论是，氧化应激是胎盘合成和释放促炎因子的有效诱导剂。大多数这些作用是通过 p38 MAPK 和核因子-κB 途径介导的，并且可以在体外被维生素 C 和 E 有效阻断。
Preeclampsia is a potentially fatal complication of human pregnancy characterized by hypertension, proteinuria, and edema. Placental oxidative stress is a key element in the pathogenesis of the syndrome and results in the release of a cocktail of factors, including proinflammatory cytokines and apoptotic debris, that in turn cause activation of the maternal endothelium. The intermediary molecular mechanisms underlying this release are unknown, but they represent a potential target for therapeutic interventions. We examined activation of signaling pathways during hypoxia-reoxygenation of villous explants in vitro. Hypoxia-reoxygenation activated the p38 and stress-activated protein kinase mitogen-activated protein kinase (MAPK) and the nuclear factor-κB pathways. Downstream consequences included increased tissue concentrations and secretion of tumor necrosis factor-α and interleukin-1β, increased expression of cyclooxygenase-2, and increased apoptosis. Administration of vitamins C and E to explants blocked activation of the p38 and stress-activated protein kinase MAPK and nuclear factor-κB pathways. Vitamin administration or p38 pathway inhibition also reduced cyclooxygenase-2 expression, tumor necrosis factor-α and interleukin-1β secretion, and the levels of apoptosis. We conclude that oxidative stress is a potent inducer of placental synthesis and release of proinflammatory factors. Most of these effects are mediated through the p38 MAPK and nuclear factor-κB pathways and can be effectively blocked by vitamins C and E in vitro.
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影响因子：
168.9
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通讯作者：
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