p38丝裂原活化蛋白激酶在间歇性缺氧/复氧过程中NF-κB信号传导中的关键作用。
A critical role for p38 map kinase in NF-kappaB signaling during intermittent hypoxia/reoxygenation.
作者信息
Ryan Silke, McNicholas Walter T, Taylor Cormac T
机构信息
School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
出版信息
Biochem Biophys Res Commun. 2007 Apr 13;355(3):728-33. doi: 10.1016/j.bbrc.2007.02.015. Epub 2007 Feb 9.
NF-kappaB-dependent inflammatory gene expression is induced by intermittent hypoxia/reoxygenation (IHR), an event that we have hypothesized may contribute to the cardiovascular pathophysiology associated with obstructive sleep apnoea syndrome (OSAS). Here, we have investigated the cellular signaling mechanisms involved. Using an established endothelial cell in vitro model, we confirm a selective activation of the pro-inflammatory transcription factor NF-kappaB over the adaptive hypoxia-inducible factor-1 (HIF-1) in IHR-stimulated bovine aortic endothelial cells. IHR activates the I-kappaB kinase (IKK) complex, leading to phosphorylation/degradation of I-kappaB alpha. IHR activates p38 MAPK and pharmacological inhibition of p38 (using SB 203580, 10 microM) abolishes NF-kappaB activation by IHR. Furthermore, depletion of p38 using siRNA significantly reduces IHR-induced NF-kappaB activity. Thus, IHR activates NF-kappaB in an IKK-dependent manner signaled at least in part via activation of p38 MAPK.
间歇性低氧/复氧（IHR）可诱导核因子κB（NF-κB）依赖性炎症基因表达，我们推测这一事件可能与阻塞性睡眠呼吸暂停综合征（OSAS）相关的心血管病理生理学有关。在此，我们研究了其中涉及的细胞信号传导机制。利用已建立的体外内皮细胞模型，我们证实在IHR刺激的牛主动脉内皮细胞中，促炎转录因子NF-κB比适应性低氧诱导因子-1（HIF-1）有选择性激活。IHR激活IκB激酶（IKK）复合物，导致IκBα磷酸化/降解。IHR激活p38丝裂原活化蛋白激酶（p38 MAPK），用SB 203580（10微摩尔）对p38进行药理学抑制可消除IHR对NF-κB的激活。此外，使用小干扰RNA（siRNA）耗尽p38可显著降低IHR诱导的NF-κB活性。因此，IHR以IKK依赖性方式激活NF-κB，至少部分是通过激活p38 MAPK发出信号。
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