Effect of hyperketonemia (Acetoacetate) on nuclear factor-κB and p38 mitogen-activated protein kinase activation mediated intercellular adhesion molecule 1 upregulation in endothelial cells.

Effect of hyperketonemia (Acetoacetate) on nuclear factor-κB and p38 mitogen-activated protein kinase activation mediated intercellular adhesion molecule 1 upregulation in endothelial cells.
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高酮血症(乙酰乙酸)对核因子-κB 和 p38 丝裂原激活蛋白激酶激活介导的内皮细胞中细胞间粘附分子 1 上调的影响。

DOI:
10.1089/met.2014.0101
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发表时间:
2015
影响因子:
2.1
通讯作者:
Jain,SushilK
Jain,SushilK
中科院分区:
医学4区
文献类型:
--
作者:
Rains,JustinL;Jain,SushilK

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Background:Hyperketonemia is a pathological condition observed in patients with type 1 diabetes and ketosis-prone diabetes (KPD), which results in increased blood levels of acetoacetate (AA) and β-hydroxybutyrate (BHB). Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. We examined the hypothesis that hyperketonemia activates the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that regulate intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells.Methods:Human umbilical vein endothelial cells (HUVECs) were cultured with AA (0–8 mM) or BHB (0–10 mM) for 0–24 hr. Western blotting was used to determine NF-κB activation in whole-cell lysates. ICAM-1 expression was measured using flow cytometry.Results:Results show a 2.4-fold increase in NF-κB activation in cells treated with 8 mM AA compared to the control. BHB had little or no effect on NF-κB activation. Pretreatment with a reactive oxygen species (ROS) inhibitor [N-acetyl-l-cysteine (NAC)] reduced NF-κB to near-control levels. The expression of AA-induced ICAM-1 was significantly reduced when cells were pretreated with either NAC or p38 MAPK inhibitor.Conclusions:These results suggest that NF-κB and p38 MAPK mediate upregulation of ICAM-1 expression in endothelial cells exposed to elevated levels of AA, which may contribute to the development of vascular disease in diabetes.
皮肤成纤维细胞和大鼠主动脉平滑肌细胞中的弹性蛋白酶样酶。
DOI: 10.1016/0309-1651(80)90064-8
发表时间: 1980
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期刊:
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DOI: 10.1111/1523-1747.ep12546063
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