Role of NADH: quinone oxidoreductase-1 in the tight junctions of colonic epithelial cells
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NADH:quinone oxidoreductase 1 (NQO1) is known to beinvolved in the regulation of energy synthesis and metabolism,and the functional studies of NQO1 have largely focused onmetabolic disorders. Here, we show for the first time thatcompared to NQO1-WT mice, NQO1-KO mice exhibited amarked increase of permeability and spontaneous inflammationin the gut. In the DSS-induced colitis model, NQO1-KO miceshowed more severe inflammatory responses than NQO1-WTmice. Interestingly, the transcript levels of claudin andoccludin, the major tight junction molecules of gut epithelialcells, were significantly decreased in NQO1-KO mice. Thecolons of NQO1-KO mice also showed high levels of reactiveoxygen species (ROS) and histone deacetylase (HDAC) activity,which are known to affect transcriptional regulation. Takentogether, these novel findings indicate that NQO1 contributesto the barrier function of gut epithelial cells by regulating thetranscription of tight junction molecules.
Abstract
NADH:quinone oxidoreductase 1 (NQO1) is known to beinvolved in the regulation of energy synthesis and metabolism,and the functional studies of NQO1 have largely focused onmetabolic disorders. Here, we show for the first time thatcompared to NQO1-WT mice, NQO1-KO mice exhibited amarked increase of permeability and spontaneous inflammationin the gut. In the DSS-induced colitis model, NQO1-KO miceshowed more severe inflammatory responses than NQO1-WTmice. Interestingly, the transcript levels of claudin andoccludin, the major tight junction molecules of gut epithelialcells, were significantly decreased in NQO1-KO mice. Thecolons of NQO1-KO mice also showed high levels of reactiveoxygen species (ROS) and histone deacetylase (HDAC) activity,which are known to affect transcriptional regulation. Takentogether, these novel findings indicate that NQO1 contributesto the barrier function of gut epithelial cells by regulating thetranscription of tight junction molecules.
참고문헌 (28)
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