Circadian clock control of Nox4 and reactive oxygen species in the vasculature.
Circadian clock control of Nox4 and reactive oxygen species in the vasculature.
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DOI：
10.1371/journal.pone.0078626
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rudic RD
中科院分区：
文献类型：
--
作者：
Anea CB;Zhang M;Chen F;Ali MI;Hart CM;Stepp DW;Kovalenkov YO;Merloiu AM;Pati P;Fulton D;Rudic RD
最近的研究表明，生物钟紊乱与动脉结构和血管僵硬的病理重塑有关。此外，慢性昼夜节律中断与内皮反应和信号传导功能障碍有关。活性氧已成为血管病理的关键调节因子。之前，我们已经证明了生物钟功能障碍通过eNOS解耦加剧了超氧化物的产生。迄今为止，生物钟突变对血管NADPH氧化酶表达和功能的影响尚不清楚。当前研究的目的是确定生物钟是否控制血管Nox4的表达和过氧化氢在动脉中的形成，特别是在内皮细胞和血管平滑肌细胞中。在昼夜节律失调小鼠（Bmal1-KO小鼠）的主动脉中，过氧化氢和Nox4的表达增加。此外，Nox4基因启动子可被核心昼夜节律转录因子激活。最后，在同步培养的人内皮细胞中，Nox4基因表达表现出节律性振荡。这些数据表明，生物钟在控制Nox4中起着重要作用，生物钟的破坏导致随后的反应氧的产生。
Recent studies have shown that circadian clock disruption is associated with pathological remodeling in the arterial structure and vascular stiffness. Moreover, chronic circadian disruption is associated with dysfunction in endothelial responses and signaling. Reactive oxygen species have emerged as key regulators in vascular pathology. Previously, we have demonstrated that circadian clock dysfunction exacerbates superoxide production through eNOS uncoupling. To date, the impact of circadian clock mutation on vascular NADPH oxidase expression and function is not known. The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle cells. In aorta, there was an increase in hydrogen peroxide and Nox4 expression in mice with a dysfunctional circadian rhythm (Bmal1-KO mice). In addition, the Nox4 gene promoter is activated by the core circadian transcription factors. Lastly, in synchronized cultured human endothelial cells, Nox4 gene expression exhibited rhythmic oscillations. These data reveal that the circadian clock plays an important role in the control of Nox4 and disruption of the clock leads to subsequent production of reaction oxygen species.
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影响因子：
20.1
作者：
Durgan DJ;Pulinilkunnil T;Villegas-Montoya C;Garvey ME;Frangogiannis NG;Michael LH;Chow CW;Dyck JR;Young ME
通讯作者：
Young ME
影响因子：
5.5
作者：
Hwang, JN;Kleinhenz, DJ;Hart, CM
通讯作者：
Hart, CM
DOI：
10.1152/ajpheart.00238.2012
发表时间：
2012-08-01
影响因子：
4.8
作者：
Lefta, Mellani;Campbell, Kenneth S.;Esser, Karyn A.
通讯作者：
Esser, Karyn A.
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.