Transcription factors Nrf2 and NF-κB contribute to inflammation and apoptosis induced by intestinal ischemia-reperfusion in mice

Meng,Qing-Tao; Chen,Rong; Chen,Cheng; Su,Ke; Li,Wei; Tang,Ling-Hua; Liu,Hui-Min; Xue,Rui; Sun,Qian; Leng,Yan; Hou,Jia-Bao; Wu,Yang; Xia,Zhong-Yuan

doi:10.3892/ijmm.2017.3170

Transcription factors Nrf2 and NF-κB contribute to inflammation and apoptosis induced by intestinal ischemia-reperfusion in mice

Authors:
- Qing-Tao Meng
- Rong Chen
- Cheng Chen
- Ke Su
- Wei Li
- Ling-Hua Tang
- Hui-Min Liu
- Rui Xue
- Qian Sun
- Yan Leng
- Jia-Bao Hou
- Yang Wu
- Zhong-Yuan Xia
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Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Anesthesiology, Renmin Hospital of Shiyan City, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: October 2, 2017 https://doi.org/10.3892/ijmm.2017.3170
Pages: 1731-1740
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intestinal ischemia/reperfusion (IIR) is a common pathological event associated with intestinal injury and apoptosis with high mortality. Nuclear factor (NF)-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with NF-κB and has a vital anti-inflammatory effect. However, whether Nrf2 has a role in IIR-induced apoptosis and the possible underlining mechanisms, such as modulation of the inflammation regulation pathway, have remained to be fully elucidated. In the present study, IIR was identified to cause significant intestinal injury and apoptosis, with high expression levels of inflammatory cytokines, as well as the apoptotic proteins B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and caspase-3, while simultaneously decreasing the protein levels of Bcl-2. The effect was more pronounced after pretreatment of the animals with all-trans retinoic acid or brusatol, potent inhibitors of Nrf2. t-Butylhydroquinone, an Nrf2 activator, significantly attenuated IIR-induced intestinal injury and apoptosis, with inhibition of the overexpression of the inflammatory cytokines, Bax and caspase-3 protein and partial restoration of Bcl-2 protein expression. Taken together, these results indicated that increased Nrf2 expression reduced IIR-induced intestinal apoptosis and that the protective function of Nrf2 may be based on its anti-inflammatory effects through the inhibition of the NF-κB pathway.

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