Lipoxin A4 protects against spinal cord injury via regulating Akt/nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 signaling

Lu, Tan; Wu, Xuejian; Wei, Na; Liu, Xiaotan; Yingfeng, Zhou; Shang, Chunfeng; Duan, Yongzhuang; Dong, Yan

doi:10.1016/j.biopha.2017.10.092

Cited by 30 publications

(15 citation statements)

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“…Heme oxygenase (HO) is a highly conserved enzyme involved in the secondary injury process, it degrades heme into biliverdin, carbon monoxide, and free iron (Fe 3+ ). Genetic or pharmacological upregulation of HO-1 activity preserves spinal cord function and restrains the neuron death after SCI [ [8] , [9] , [10] , [11] , [12] , [13] ]. As a heme degradation product, carbon monoxide (CO) has been proved to have various bioactivity such as anti-inflammatory, anti-apoptotic and antioxidant in low concentration [ [14] , [15] , [16] ], which might explains the HO-1-induced protection following SCI.…”

Section: Introductionmentioning

confidence: 99%

Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation

et al. 2019

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BackgroundGenetic overexpression or pharmacological activation of heme oxygenase (HO) are identified as potential therapeutic target for spinal cord injury (SCI); however, the role of carbon monoxide (CO), which is a major product of haem degenerated by HO, in SCI remains unknown. Applying hemin or chemicals which may regulate HO expression or activity to increase CO production are inadequate to elaborate the direct role of CO. Here, we assessed the effect of CO releasing molecule-3 (CORM-3), the classical donor of CO, in SCI and explained its possible protective mechanism.MethodsRat SCI model was performed with a vascular clip (30 g) compressing at T9 vertebral level for 1 min and CO was delivered immediately after SCI by CORM-3. The neurological deficits and neuron survival were assessed. Inflammasome and inositol-requiring enzyme 1 (IRE1) pathway were measured by western blot and immunofluorescence. For in vitro study, oxygen glucose deprivation (OGD) simulated the SCI-inflammasome change in cultured the primary neurons.FindingsCORM-3 suppressed inflammasome signaling and pyroptosis occurrence, which consequently alleviated neuron death and improved motor functional recovery following SCI. As a pivotal sensor involving in endoplasmic reticulum stress-medicated inflammasome signaling, IRE1 and its downstream X-box binding protein 1 (XBP1) were activated in SCI tissues as well as in OGD neurons; while inhibition of IRE1 by STF-083010 in SCI rats or by si-RNA in OGD neurons suppressed inflammasome signaling and pyroptosis. Interestingly, the SCI/OGD-stimulated IRE1 activation was attenuated by CORM-3 treatment.InterpretationsCO may alleviate neuron death and improve motor functional recovery in SCI through IRE1 regulation, and administration of CO could be a promising therapeutic strategy for SCI.

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Section: Introductionmentioning

confidence: 99%

Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation

et al. 2019

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“…Lipoxin A4 (LXA4) possesses a good anti-inflammatory effect on the respiratory tract, intestines, and nephridium [12][13][14][15][16]. It was observed that LXA4 alleviated inflammation and neuropathic pain after SCI [17,18]. Furthermore, LXA4 can reduce the level of oxidative stress in spinal cord ischemia and hypoxia injury [19].…”

Section: Introductionmentioning

confidence: 99%

The Lipoxin A4 Receptor Agonist BML-111 Alleviates Inflammatory Injury and Oxidative Stress in Spinal Cord Injury

Liu

Peng

2020

Med Sci Monit

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Departmental sources Background: Spinal cord injury (SCI) has a high incidence and causes serious harm. Lipoxin A4 (LXA4) receptor agonist BML-111 was reported to regulate inflammation and oxidative stress. The goal of this study was to assess whether BML-111 could protect against SCI by suppressing inflammation and oxidative stress. Material/Methods: We developed a rat SCI model, then BML-111 was intraperitoneally injected into SCI rats to observe the BML-111 function. The pathological changes of SCI were observed with hematoxylin and eosin (HE) staining. Motor function of rats were assessed by the modified Tarlov's scale. ELISA was used to assess the changes in levels of TNF-a, IL-1b, and IL-6. Western blot analysis was performed to assess the expressions of TNF-a, IL-1b, IL-6, Bcl2, Bax, and cleaved caspase3 in spinal cord tissue. TOS and TAS in rat serum were detected by xylenol orange method and ABTS method, respectively. The apoptotic cells in spinal cord tissue were observed with TUNEL assay. Results: The results indicated that BML-111 effectively improved the SCI and motor function of rats. BML-111 treatment decreased the levels of TNF-a, IL-1b, and IL-6 in serum and spinal cord tissue, as well as decreasing the levels of TOS and TAS and cell apoptosis. Conclusions: BML-111 alleviated inflammation and oxidative stress in SCI rats.

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“…MMPs expression is regulated by NF‐κB, Akt, and Gsk‐3β . Loss of E‐cadherin and β‐catenin in first‐trimester EVT is associated with increased trophoblast invasiveness .…”

Section: Discussionmentioning

confidence: 99%

Lipoxin A4 interferes with embryo implantation via suppression of epithelial‐mesenchymal transition

Zhao

Zhou

et al. 2019

American J Rep Immunol

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Problem To test whether lipoxin A4 (LXA4) interferes with embryo implantation via suppression of epithelial‐mesenchymal transition (EMT). Method of study We developed a mouse model of LXA4 blocking embryo implantation and detected the indicators of EMT to confirm that LXA4 inhibits EMT might be a mechanism of interfering with the embryo implantation. We detected integrin‐linked kinase (ILK), N‐formylpeptide receptor 2 (FPR2), vascular endothelial growth factor, matrix metalloproteinases (MMPs), Akt, GSK3β, NF‐ĸB, twist, vimentin, fibronectin, and β‐catenin mRNA expression using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time RT‐PCR; localized protein expression using immunohistochemistry and Western blotting assay; MMPs activity assay by gelatin zymography; and the status of implantation in pregnant animals assessed by pontamine blue reaction test. Results Preimplantation administration of LXA4 resulted in implantation failure. LXA4 has a time‐ and dose‐dependent effect on embryo implantation. Day 0.5 after fertilization is the most effective time to use LXA4 to block embryo implantation. (a) LXA4 reduced endometrial stroma edema; (b) LXA4 inhibited the activity of MMP9 and significantly upregulated the expression of β‐catenin, and downregulated the expression of vimentin, fibronectin, twist, NF‐κB, Akt, and Gsk‐3β in the endometrium and TEV‐1 cells; (c) LXA4 upregulated the expression of FPR2, and downregulated the expression of ILK; FPR2‐overexpressing had an inhibitory effect on ILK in TEV‐1 cells. Conclusion LXA4 inhibits EMT which attenuates ILK action by enhancing FPR2; therefore, this might be a mechanism of interfering with embryo implantation.

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Lipoxin A4 protects against spinal cord injury via regulating Akt/nuclear factor (erythroid-derived 2)-like 2/heme oxygenase-1 signaling

Cited by 30 publications

References 29 publications

Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation

Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation

The Lipoxin A4 Receptor Agonist BML-111 Alleviates Inflammatory Injury and Oxidative Stress in Spinal Cord Injury

Lipoxin A4 interferes with embryo implantation via suppression of epithelial‐mesenchymal transition

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