FBXW5 aggravates hepatic ischemia/reperfusion injury via promoting phosphorylation of ASK1 in a TRAF6-dependent manner

Li, Tingting; Luo, Yunhai; Yang, Hang; Chai, Hao; Lei, Zilun; Peng, Dadi; Wu, Zhongjun; Huang, Zuotian

doi:10.1016/j.intimp.2021.107928

Cited by 18 publications

(26 citation statements)

References 25 publications

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“…Moreover, regulation of TRAF6 at the modi cation level has a certain effect [10,16,38]. For instance, we previously found that F-box/WD repeat-containing protein 5 (FBXW5) as a newly discovered E3 ligand of apoptotic signal-regulating kinase 1 (ASK1) promoted the TRAF6-K63 chain by enhancing the phosphorylation of ASK1 [10]. Likewise, other research reported that TRAF6 ubiquitinating activity is required for tollinteracting protein (Tollip) commanding ASK1-MAPK axis in liver I/R injury [39].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, inhibitor of nuclear factor kappa-B kinase (IKK) complex phosphorylates inhibitor of NF-κB (IκBα), causing sequential disintegration and activation of canonical IκBα/nuclear factor kappa B (NF-κB) in Kupffer cells. Phosphorylation and translocation of NF-κB p65 generates increased secretion of in ammatory cytokines and chemokines, which induce the stress and death of hepatocytes as we previous explored [6,10]. However, the speci c mechanism of IKK complex has not yet fully disclosed because of the subunit diversity and functional complexity of IKK comprising two catalytic subunits (IKKα and IKKβ) and one regulatory subunit (IKKγ).…”

Section: Introductionmentioning

confidence: 99%

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TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

Yang

Huang

Luo

et al. 2022

Preprint

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Background Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes among various liver surgery. However, there is still a lack of strategies against hepatic I/R injury because of the unrevealed inner mechanism. The present study aimed to identify a potential strategy for hepatic I/R injury and provide the fundamental experimental basis. Results Here we report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through reinforcement of IKK-induced inflammation following dual patterns. Mechanically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) thus igniting K63 ubiquitination, eventually leading to the phosphorylation of IKKβ. Meanwhile, TRIM37 enhances translocation of IKKγ, a regulatory subunit of IKK complex, from nucleus to cytoplasm thereby stabilizing cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK could rescue the function of TRIM37 both in vivo and in vitro. Conclusion Collectively, the present study discloses the critical role of TRIM37 facilitating hepatic I/R injury by activating IKK axis. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

Yang

Huang

Luo

et al. 2022

Preprint

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“…TRIZOL (Beyotime) was used for RNA isolation from either cells or tissues based on our previous research [6,10]. Relative expression of CXC chemokine ligand 10 (CXCL-10), C-C Motif Chemokine ligand 2 (MCP1, CCL-2), CXCL-2 and IL-10 was normalized to β-actin.…”

Section: Quantitative Real-time Pcr (Qrt-pcr)mentioning

confidence: 99%

“…All interference sequences are listed in Table 3. The speci c inhibitor of TRAF6-Ubc13 interaction, C25-140, was administered 2 h before subsequent treatment at 20 µM based on our previous experience [6,7,10]. The speci c inhibitor of IKKβ, IMD0354, was administered 12 h before subsequent treatment at 10 µM based on our previous experience [6, 7, 10].…”

Section: Transfection and Administration In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

Yang

Huang

Luo

et al. 2022

Preprint

Self Cite

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Hepatic ischemia/reperfusion (I/R) injury is one of the major pathological processes among various liver surgery. However, there is still a lack of strategies against hepatic I/R injury because of the unrevealed inner mechanism. Here we report that tripartite motif containing 37 (TRIM37) aggravates hepatic I/R injury through reinforcement of IKK-induced inflammation following dual patterns. Mechanically, TRIM37 directly interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) thus igniting K63 ubiquitination, eventually leading to the phosphorylation of IKKβ. Meanwhile, TRIM37 enhances translocation of IKKγ, a regulatory subunit of IKK complex, from nucleus to cytoplasm thereby stabilizing cytoplasmic IKK complex and prolonging the duration of inflammation. Inhibition of IKK could rescue the function of TRIM37 both in vivo and in vitro. Collectively, the present study discloses the critical role of TRIM37 facilitating hepatic I/R injury by activating IKK axis. Targeting TRIM37 might be potential for treatment against hepatic I/R injury.

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AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis

Zhang,

Li,

Liu

2024

Drug Development Research

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Cerebral ischemia/reperfusion injury is one of the main causes of neuronal damage. Neuron ferroptosis and microglia polarization are considered as critical processes during cerebral ischemia/reperfusion. Adipocyte enhancer‐binding protein 1 (AEBP1) usually acts as a transcriptional repressor which is involved in various diseases. However, it is still remains unknown whether AEBP1 could have important roles in regulating the neuron ferroptosis and microglia polarization in cerebral ischemia/reperfusion injury. The oxygen‐glucose deprivation and reperfusion (OGD/R)‐treated cells and middle cerebral artery occlusion (MCAO)‐treated mice were used as in vitro and in vivo models. The differentially expressed factors were analyzed according to GEO datasets. Relative mRNA and protein expression levels were detected by qRT‐PCR and western blot analysis. Cell viability was measured by CCK‐8 assay. ROS, GSH and iron contents were detected using specifical assay kits. CD26 and CD206 levels were measured by immunofluorescence assay. Inflammatory cytokines were detected by ELISA. The association between AEBP1 and PRKCA was assessed by luciferase reporter and ChIP analyses. The neuron damage in mice was analyzed by TTC staining and neurological deficit score. Transcription factor AEBP1 was increased in OGD/R‐treated HT22 and BV2 cells. AEBP1 silencing attenuated OGD/R‐induced HT22 cell ferroptosis through increasing cell viability, GSH and GPX4 levels, and decreasing ROS, iron and ACSL4 levels. AEBP1 knockdown promoted microglia M2 polarization by increasing CD206‐positive cells and Arg‐1 level, and reducing iNOS, TNF‐α, IL‐1β and IL‐6 levels in BV2 cells. AEBP1 transcriptionally repressed PRKCA expression, and further regulated PI3K/Akt signaling activation. Inhibition of PRKCA or PI3K/Akt reversed the effects of AEBP1 silencing on neuron ferroptosis and microglia M2 polarization. AEBP1 downregulation attenuated neuronal damage by decreasing infarct size and deficit scores in MCAO‐treated mice. AEBP1 silencing mitigated neuron ferroptosis and promoted microglia M2 polarization through increasing PRKCA and activating PI3K/Akt signaling, indicating the potentially protective action of AEBP1 knockdown in cerebral ischemia/reperfusion injury.

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FBXW5 aggravates hepatic ischemia/reperfusion injury via promoting phosphorylation of ASK1 in a TRAF6-dependent manner

Cited by 18 publications

References 25 publications

TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

TRIM37 exacerbates hepatic ischemia/reperfusion injury by facilitating IKK pathway through TRAF6 stimulation and IKKγ translocation

AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA‐PI3K‐Akt Axis

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