Nrf2/ARE pathway activation, HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling

Li, Lingrui; Dong, Hui; Song, Erqun; Xu, Xiaoyu; Liu, Lichao; Song, Yang

doi:10.1016/j.cbi.2013.12.005

Cited by 204 publications

(116 citation statements)

References 61 publications

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“…Many studies have demonstrated its role in IR injury in organs including kidney [37]. Interestingly, in the PPI network, Hmox1 interacted with NAD(P)H dehydrogenase, quinone 1 (Nqo1) which was also an antioxidant protein that regulated ROS generation [38]. Importantly, Gang et al [39] have suggested that Nqo1 has a protective role against renal injury induced by IR.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Wang

Tang²,

Ye³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Ischemia-reperfusion (IR) injury in the kidney is a major cause of acute kidney injury in humans. However, the molecular mechanisms responsible for the progression of kidney IR injury still need to be explored. In this study, we aimed to explore the underlying genes and pathways associated with kidney IR injury. Methods: Gene microarray of GSE27274 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between kidney IR injury and kidney IR rat samples were analyzed. Gene Ontology biological process (BP) and pathway enrichment analyses of DEGs were performed, followed by protein-protein interaction (PPI) network construction. Results: A total of 88 up-regulated and 102 down-regulated DEGs were identified. The up-regulated DEGs including FK506 binding protein 1A (Fkb1a) were mainly enriched in biological processes (BPs) related to protein ubiquitination. The down-regulated DEGs including complement component 5 (C5) were enriched in complement and coagulation cascades pathway. Choline phosphotransferase 1 (Chpt1) was enriched in glycerophospholipid metabolism pathway. In the PPI network, heme oxygenase (decycling) 1 (Hmox1) was as a hub gene that interacted with the maximum nodes. Conclusions: DEGs of Fkb1a, C5, Chpt1, and Hmox1, as well as complement and coagulation cascades pathway, glycerophospholipid metabolism pathway, and BP terms related to protein ubiquitinatione may be the potential targets for diagnosis and treatment of kidney IR injury.

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Section: Discussionmentioning

confidence: 99%

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Wang

Tang²,

Ye³

et al. 2016

Kidney Blood Press Res

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“…Thus it is of interest to investigate the roles of other junction proteins, like ␣-catenin, ␤-catenin, and p120, in regulating junction breakdown mediated by PCB quinone treatment in the future studies. PCB29-pQ has been shown to upregulate reactive oxygen species (ROS) in cells (36). Since vascular endothelial integrity can be altered by ROS, PCB29-pQ may increase endothelial permeability by promoting ROS generation (16).…”

Section: Discussionmentioning

confidence: 99%

Polychlorinated biphenyl quinone induces endothelial barrier dysregulation by setting the cross talk between VE-cadherin, focal adhesion, and MAPK signaling

Zhang

Feng

Bai

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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biphenyl quinone induces endothelial barrier dysregulation by setting the cross talk between VE-cadherin, focal adhesion, and MAPK signaling. Am J Physiol Heart Circ Physiol 308: H1205-H1214, 2015. First published March 13, 2015; doi:10.1152/ajpheart.00005.2015.-Environmental hazardous material polychlorinated biphenyl (PCB) exposure is associated with vascular endothelial dysfunction, which may increase the risk of cardiovascular diseases and cancer metastasis. Our previous studies illustrated the cytotoxic, antiproliferative, and genotoxic effects of a synthetic, quinone-type, highly reactive metabolite of PCB, 2,3,5-trichloro-6-phenyl-[1,4]benzoquinone (PCB29-pQ). Here, we used it as the model compound to investigate its effects on vascular endothelial integrity and permeability. We demonstrated that noncytotoxic doses of PCB29-pQ induced vascular endothelial (VE)-cadherin junction disassembly by increasing the phosphorylation of VE-cadherin at Y658. We also found that focal adhesion assembly was required for PCB29-pQ-induced junction breakdown. Focal adhesion site-associated actin stress fibers may serve as holding points for cytoskeletal tension to regulate the cellular contractility. PCB29-pQ exposure promoted the association of actin stress fibers with paxillincontaining focal adhesion sites and enlarged the size/number of focal adhesions. In addition, PCB29-pQ treatment induced phosphorylation of paxillin at Y118. By using pharmacological inhibition, we further demonstrated that p38 activation was necessary for paxillin phosphorylation, whereas extracellular signal-regulated kinases-1/2 activation regulated VE-cadherin phosphorylation. In conclusion, these results indicated that PCB29-pQ stimulates endothelial hyperpermeability by mediating VE-cadherin disassembly, junction breakdown, and focal adhesion formation. Intervention strategies targeting focal adhesion and MAPK signaling could be used as therapeutic approaches for preventing adverse cardiovascular health effects induced by environmental toxicants such as PCBs.

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“…Nrf2 binds to the antioxidant response element (ARE) in the promoter region of several genes, and it is an upstream regulator of the encoding of antioxidative proteins, such as heme oxygenase 1 (HO-1), which antagonize reactive oxygen species (ROS)-induced oxidative stress [7,8].…”

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Zhou

Che

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ischemia-reperfusion (I/R) adversely affects the intestinal mucosa. The major mechanisms of I/R are the generation of reactive oxygen species (ROS) and apoptosis. Salvianolic acid A (SalA) is suggested to be an effective antioxidative and antiapoptotic agent in numerous pathological injuries. The present study investigated the protective role of SalA in I/R of the intestine. Methods: Adult male Sprague-Dawley rats were subjected to intestinal I/R injury in vivo. In vitro experiments were performed in IEC-6 cells subjected to hypoxia/ reoxygenation (H/R) stimulation to simulate intestinal I/R. TNF-α, IL-1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay. Malondialdehyde and myeloperoxidase and glutathione peroxidase levels were measured using biochemical analysis. Apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining or flow cytometry in vivo and in vitro. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. Western blotting was performed to determine the expression of heme oxygenase-1 (HO-1), Nrf2 and proteins associated with apoptosis. The mRNA expressions of Nrf2 and HO-1 were detected by quantitative real-time polymerase chain reaction in vivo and in vitro. Results: Malondialdehyde level and myeloperoxidase and glutathione peroxidase, TNF-α, IL-1β, and IL-6 levels group in intestinal tissue decreased significantly in the SalA pretreatment groups compared to the I/R group. SalA markedly abolished intestinal injury compared to the I/R group. SalA significantly attenuated apoptosis and increased Nrf2/HO-1 expression in vivo and in vitro. However, Nrf2 siRNA treatment partially abrogated the above mentioned effects of SalA in H/R-induced ROS and apoptosis in IEC-6 cells. Conclusion: The present study demonstrated that SalA ameliorated oxidation, inhibited the release of pro-inflammatory cytokines and alleviated apoptosis in I/R-induced injury and that these protective effects may partially occur via regulation of the Nrf2/ HO-1 pathways.

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Nrf2/ARE pathway activation, HO-1 and NQO1 induction by polychlorinated biphenyl quinone is associated with reactive oxygen species and PI3K/AKT signaling

Cited by 204 publications

References 61 publications

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Polychlorinated biphenyl quinone induces endothelial barrier dysregulation by setting the cross talk between VE-cadherin, focal adhesion, and MAPK signaling

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

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