Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation

Li, Jing; Wang, Hongyan; Zheng, Zhaohong; Luo, Lin; Wang, Peng; Liu, Kaihua; Namani, Akhileshwar; Jiang, Zhinong; Wang, Xiu Jun; Tang, Xiuwen

doi:10.1016/j.freeradbiomed.2018.07.002

Cited by 58 publications

(26 citation statements)

References 41 publications

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“…On one hand, MKP‐1 enhances Nrf2/ARE signaling by directly interacting with the Neh2 domain of Nrf2 and increases its stability; on the other hand, MKP‐1 is an Nrf2 target gene. Nrf2 induces MKP‐1 transcription by binding to the ARE site in the promoter of MKP‐1 . The finding in this study implies that phosphorylation and degradation of Nrf2 by P‐JNK not only causes dysfunction of the ARE‐cytoprotective system, but may also repress MKP‐1 signaling, leading to prolonged activation of JNK.…”

Section: Discussionsupporting

confidence: 50%

c‐Jun NH2‐Terminal Protein Kinase Phosphorylates the Nrf2‐ECH Homology 6 Domain of Nuclear Factor Erythroid 2–Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen‐Induced Liver Injury in Mice

et al. 2020

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BaCKgRoUND aND aIMS: Acetaminophen (APAP) overdose induces severe liver injury and hepatic failure. While the activation of c-Jun NH 2 -terminal kinase ( JNK) has been implicated as a mechanism in APAP-induced liver injury, the hepatic defense system controlled by nuclear factor erythroid 2-related factor 2 (Nrf2) plays a central role in the mitigation of APAP toxicity. However, the link between the two signaling pathways in APAP-induced liver injury (AILI) remains unclear. appRoaCH aND ReSUltS: In this study, we demonstrated that the activation of JNK in mouse liver following exposure to APAP was correlated with the phosphorylation of Nrf2 and down-regulation of the antioxidant response element (ARE)-driven genes, NAD(P)H:quinone dehydrogenase 1, glutathione S-transferase α3, glutathione S-transferase M1, glutathione S-transferase M5, and aldo-keto reductase 1C. The JNK inhibitor, SP600125, or knockdown of JNK by infection of adenovirus expressing JNK small interfering RNA, ameliorated the APAP induced liver toxicity, and inhibited the phosphorylation of Nrf2 and down-regulation of detoxifying enzymes by stabilizing the transcription factor. Mechanistically, JNK antagonized Nrf2-and ARE-driven gene expression in a Kelch-like ECH-associated protein 1-independent manner. Biochemical analysis revealed that phosphorylated JNK (P-JNK) directly interacted with the Nrf2-ECH homology (Neh) 1 domain of Nrf2 and phosphorylated the serine-aspartateserine motif 1 (SDS1) region in the Neh6 domain of Nrf2.CoNClUSIoNS: Mass spectrometric analysis identified serine 335 in the SDS1 region of mNrf2 as the major phosphorylation site for modulation of Nrf2 ubiquitylation by P-JNK. This study demonstrates that Nrf2 is a target of P-JNK in AILI. Our finding may provide a strategy for the treatment of AILI. (Hepatology 2020;71:1787-1801. N -acetyl-p-aminophenol (APAP; acetaminophen) is a commonly used non-narcotic analgesic drug used to reduce fever and relieve

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Section: Discussionsupporting

confidence: 50%

c‐Jun NH2‐Terminal Protein Kinase Phosphorylates the Nrf2‐ECH Homology 6 Domain of Nuclear Factor Erythroid 2–Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen‐Induced Liver Injury in Mice

et al. 2020

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“…Under peroxidative conditions, Nrf2 dissociates from the dimer and transfers to the nucleus, binding to the antioxidant responsive element ( 70 ). Binding to this promoter activates the expression of a cytoprotective enzyme, including HO-1, CAT, or SOD ( 71 ). Nrf2 upregulates the GST-A4 gene expression via the mitogen-activated protein kinase pathway to protect against UC ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of Gloeostereum�incarnatum on ulcerative colitis via modulation of Nrf2/NF‑κB signaling in C57BL/6 mice

Liu

Zhang

et al. 2020

Mol Med Rep

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Chronic non-specific inflammatory cell infiltration of the colon is generally considered to be the cause of ulcerative colitis (UC). Gloeostereum incarnatum (GI), a fungus rich in amino acids and fatty acids, exhibits a variety of biological functions. In the present study, GI was identified to contain 15 fatty acids, 17 amino acids and 11 metallic elements. The protective effect of GI against UC was investigated in C57BL/6 mice with UC induced by free drinking 3.5% dextran sulfate sodium (DSS). After a 21-day oral administration, GI prevented weight loss, enhancement of the disease activity index and colonic pathological alterations in mice with UC. GI reduced the levels of pro-inflammatory factors including interleukin (IL)-1β, IL-2, IL-6 and IL-12, tumor necrosis factor α and -β, interferon α and -γ, and pro-oxidative factors including reactive oxygen species and nitric oxide. In addition, it enhanced the levels of immunological factors including immunoglobulin (Ig)A, IgM and IgG, and antioxidative factors including superoxide dismutase and catalase in the serum and/or colon tissues. GI enhanced the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins and suppressed the phosphorylation of NF-κB signaling in colon tissues. Together, GI was shown to alleviate the physiological and pathological state of DSS-induced UC in mice via its antioxidant and anti-inflammatory functions, which may be associated with its modulation of the activation of Nrf2/NF-κB signaling.

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“…Previous studies have demonstrated that the inflammatory reaction would be influenced by the Nrf2/HO-1 pathways [40, 41]. Nrf2 can negatively regulate the inflammatory responses and there is a cross-talk between the Nrf2 and NF- κ B in the inflammatory responses [42, 43].…”

Section: Discussionmentioning

confidence: 99%

Imperatorin Suppresses Anaphylactic Reaction and IgE-Mediated Allergic Responses by Inhibiting Multiple Steps of FceRI Signaling in Mast Cells: IMP Alleviates Allergic Responses in PCA

Xian

Jin

Li³

et al. 2019

BioMed Research International

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This study is to investigate the effects of imperatorin (IMP) on allergic responses mediated by mast cells, both in vitro and in vivo. Passive cutaneous anaphylaxis (PCA) model was established. Histological detection was performed to assess the ear histology. ELISA and Western blot analysis were used to detect the levels of corresponding cytokines and signalling pathway proteins. IMP decreased the leakage of Evans blue and the ear thickness in the PCA models, in a dose-dependent manner, and alleviated the degranulation of mast cells. Moreover, IMP reduced the expression of TNF-α, IL-4, IL-1β, IL-8, and IL-13. Furthermore, IMP inhibited the phosphorylation levels of Syk, Lyn, PLC-γ1, and Gab2, as well as the downstream MAPK, PI3K/AKT, and NF-κB signaling pathways. In addition, IMP inhibited the mast cell-mediated allergic responses through the Nrf2/HO-1 pathway. IMP attenuates the allergic responses through inhibiting the degranulation and decreasing the expression levels of proinflammatory cytokines in the mast cells, involving the PI3K/Akt, MAPK, NF-κB, and Nrf2/HO-1 pathways.

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Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation

Cited by 58 publications

References 41 publications

c‐Jun NH2‐Terminal Protein Kinase Phosphorylates the Nrf2‐ECH Homology 6 Domain of Nuclear Factor Erythroid 2–Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen‐Induced Liver Injury in Mice

c‐Jun NH2‐Terminal Protein Kinase Phosphorylates the Nrf2‐ECH Homology 6 Domain of Nuclear Factor Erythroid 2–Related Factor 2 and Downregulates Cytoprotective Genes in Acetaminophen‐Induced Liver Injury in Mice

Protective effect of Gloeostereum�incarnatum on ulcerative colitis via modulation of Nrf2/NF‑κB signaling in C57BL/6 mice

Imperatorin Suppresses Anaphylactic Reaction and IgE-Mediated Allergic Responses by Inhibiting Multiple Steps of FceRI Signaling in Mast Cells: IMP Alleviates Allergic Responses in PCA

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