Moringa isothiocyanate-1 regulates Nrf2 and NF-κB Pathway in response to LPS-driven sepsis and inflammation
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PROVIDER: PRJNA655461 | ENA |
REPOSITORIES: ENA
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Project description:Moringa Isothiocyanate-1 (MIC-1) purified from moringa (Moringa oleifera Lam) seed extract (MSE) has been previously proved to modulate anti-inflammatory and antioxidant activities. However, the molecular mechanism remains poorly understood, particularly nothing is known about its effect on Lipopolysaccharide (LPS) induced sepsis/inflammation. Hence, we investigated whether MIC-1 can decrease acute inflammation in the LPS-induced acute inflammation/sepsis model in mice. Mice were treated orally with MIC-1 for three days before the intraperitoneal injection of LPS. MIC-1 treatment resulted in a dramatic improvement in the histopathological signs of inflammation in the liver, kidney, spleen, and colon and a significant reduction of the LPS-induced sepsis. Moreover, MIC-1 treatment significantly reduced the expression of inflammatory markers in all these organs. We also performed transcriptome analysis in vitro and in vivo in LPS induced macrophages and liver with/without MIC-1 treatment. Interestingly, there is an upregulation of inflammatory/immune response genes in LPS induced macrophages/liver, and there is downregulation of same set of genes after treating with MIC-1. Our results together indicate that MIC-1 reduces sepsis/inflammation through NF-κB and Nrf2 mediated anti-inflammatory/antioxidant signaling pathways. Research has demonstrated that chronic low-grade tissue inflammation and oxidative stress are essential factors in the development of metabolic disorders. Therefore, MIC-1 could be a new natural therapeutic strategy to treat metabolic syndrome.
2021-04-07 | GSE155738 | GEO
Project description:This study aims to investigate the effect of Moringa isothiocyanate-1 (MIC-1) derived from seeds of Moringa oleifera Lam in lipopolysaccharide (LPS)-induced muscle inflammation models. MIC-1 decreased nitric oxide production, and reduced the expression of pro-inflammatory markers, in C2C12 myoblasts. The daily oral treatment of MIC-1 (80 mg/kg) for three days significantly reduced the expression of pro-inflammatory markers (TNF-α, Ifn-α, IL-1β, IL-6) in gastrocnemius tissue of mice. Transcriptomic analysis provided insight into the inhibitory effects of MIC-1 on the LPS-induced inflammation, which suggests that MIC-1 acts via inflammation, and immunity pathways in myoblasts and skeletal muscle tissue. MIC-1 inhibited the nuclear accumulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the LPS-treated murine, which supports that MIC-1 decreases inflammation and regulates immune responses at a gene expression level in LPS-induced inflammation murine model.
2022-07-28 | GSE209706 | GEO
Project description: Not available
| S-EPMC8016325 | biostudies-literature
Project description:Unfolded protein accumulation in the lumen of endoplasmic reticulum (ER) induced by cold exposure is termed UPRER. Some mammals hibernate to overcome cold winter. We investigated whether hibernating bats are under UPRER and activate Akt, Nrf2, and NF-κB signaling pathways that are critical for cell survival against cold. Results of Western blotting showed that several UPRER marker proteins such as PERK and ATF4 had a higher abundance in torpid than in active bats. Cellular redistribution of GRP78 and a lower degree of binding between PERK and GRP78 were also seen in torpid bats, suggesting the occurrence of UPRER. Results also showed that torpid bats had a higher amount of p-Akt (Ser473), a higher ratio of p-Akt (Ser473)/Akt, a lower amount of Keap1/Nrf2 and NF-κB (p65)/I-κBα complexes, and a higher degree of NF-κB (p65) nuclear translocation than active bats, indicating simultaneous activation of Akt, Nrf2, and NF-κB during hibernation. Evidence of such activation was not observed in fasted, cold-treated, or normal mice. Using PPI network and IPA analyses, we examined the proteomes of liver and liver mitochondria of bats and found a global metabolic adjustment and survival adaptation in response to UPRER in hibernating bats. Our data provide the first molecular evidence of a complex cross talk involving Akt, Nrf2, and NF-κB via the PERK-EIF2-ATF4 regulatory axis under UPRER in bats to ensure their survival during hibernation.
2020-11-17 | PXD016109 | Pride
Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in lymphoid cells treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates. We found 242 high-confidence, NRF2-bound genomic regions and 96% of these regions contained NRF2-regulatory sequence motifs. The majority of binding sites were near potential novel members of the NRF2 pathway. Validation of selected candidate genes using parallel ChIP techniques and in NRF2-silenced cell lines indicated that the expression of about two thirds of the candidates are likely to be directly NRF2-dependent including retinoid X receptor alpha (RXRA). NRF2 regulation of RXRAhas implications for response to retinoid treatments and adipogenesis. In mouse 3T3-L1 cells SFN treatment affected Rxra expression early in adipogenesis and knockdown of Nrf2 delayed Rxra expression, both leading to impaired adipogenesis. ChIP-Seq analysis of NRF2 binding sites in human lymphoblastoid cells treated with sulforaphane or vehicle
2012-06-18 | E-GEOD-37589 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8184690 | biostudies-literature
Project description:We investigated the novel molecular mechanisms of the antioxidant and anti-inflammatory properties of S-allylmercaptocysteine (SAMC) based on a transcriptomic study in a non-alcoholic fatty liver disease (NAFLD) rat model. NAFLD was induced in Sprague-Dawley rats by feeding with a high fat diet (HFD) for 12 weeks. 200mg/kg SAMC was fed by oral gavage for 4 weeks from 9-12 week. We found that SAMC co-administration attenuated HFD-induced liver injury, including the increased serum ALT, hepatic oxidative stress and inflammation. Transcriptomic analysis revealed that SAMC dramatically induced the XRE- and ARE-driven drug metabolising enzymes (DMEs) including Akr7a3, Akr1b8, and NQO1. The nuclear translocation of the upstream regulator of xenobiotics metabolism, AhR, and regulator of antioxidant responses, Nrf2, were significantly increased by SAMC treatment. Furthermore, SAMC counteracted the effects of HFD on NF-κB/IκB and NLRP3/6 pathways with decreasing protein levels of ASC, cleaved caspase-1, IL-18 and IL-1β. These results were further verified in another mice NASH model induced by an MCD diet with SAMC co-administration. Conclusion: we propose that SAMC triggers AhR/Nrf2-mediated antioxidant responses which may further suppress the NLRP3/6 inflammasome pathway and NF-κB activation, contributing to the improvement of NAFLD/NASH.
2020-07-20 | GSE150841 | GEO
Project description:Cellular oxidative and electrophilic stress triggers a protective response in mammals regulated by NRF2 (nuclear factor (erythroid-derived) 2-like; NFE2L2) binding to DNA-regulatory sequences near stress responsive genes. Studies using Nrf2-deficient mice suggest that hundreds of genes may be regulated by NRF2. To identify human NRF2-regulated genes, we conducted ChIP-sequencing experiments in human BEAS-2B cell line treated with the dietary isothiocyanate, sulforaphane (SFN) and carried out follow-up biological experiments on candidates.
2018-06-19 | GSE75812 | GEO
Project description:Transcriptional profiling of human control and Néstor-Guillermo Progeria Syndrome (NGPS) fibroblasts and induced pluripotent stem cells (iPSCs). Somatic cell reprogramming involves rejuvenation of adult cells and relies on the ability to erase age-associated molecular marks. Accordingly, reprogramming efficiency declines with ageing, and age-associated features such as genetic instability, cell senescence or telomere shortening negatively affect this process. However, the regulatory mechanisms that constitute age-associated barriers for cell reprogramming remain largely unknown. Here, by using cells from patients with premature ageing, we demonstrate that NF-κB activation is a critical barrier for the generation of induced pluripotent stem cells (iPSCs) in ageing. We show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs generation of iPSCs by eliciting reprogramming repressors DOT1L and YY1, reinforcing cell senescence signals and down-regulating pluripotency genes. We also show that genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) and Hutchinson-Gilford Progeria Syndrome (HGPS) patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo ameliorates the accelerated ageing phenotype and extends lifespan in a progeroid animal model. Collectively, our results provide evidence for a novel role of NF-κB in the control of cell fate transitions and reinforce the interest of studying age-associated molecular impairments to implement cell reprogramming methodologies, and to identify new targets of rejuvenation strategies. Control and NGPS fibroblasts were reprogrammed. RNA was extracted and transcriptional profiling was obtained with GeneChip Human Exon 1.0 ST Arrays.
2015-07-01 | E-GEOD-65170 | biostudies-arrayexpress
Project description:Transcriptional profiling of human control and Néstor-Guillermo Progeria Syndrome (NGPS) mesenchymal stem cells (MSCs). Somatic cell reprogramming involves rejuvenation of adult cells and relies on the ability to erase age-associated molecular marks. Accordingly, reprogramming efficiency declines with ageing, and age-associated features such as genetic instability, cell senescence or telomere shortening negatively affect this process. However, the regulatory mechanisms that constitute age-associated barriers for cell reprogramming remain largely unknown. Here, by using cells from patients with premature ageing, we demonstrate that NF-κB activation is a critical barrier for the generation of induced pluripotent stem cells (iPSCs) in ageing. We show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs generation of iPSCs by eliciting reprogramming repressors DOT1L and YY1, reinforcing cell senescence signals and down-regulating pluripotency genes. We also show that genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo Progeria Syndrome (NGPS) and Hutchinson-Gilford Progeria Syndrome (HGPS) patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo ameliorates the accelerated ageing phenotype and extends lifespan in a progeroid animal model. Collectively, our results provide evidence for a novel role of NF-κB in the control of cell fate transitions and reinforce the interest of studying age-associated molecular impairments to implement cell reprogramming methodologies, and to identify new targets of rejuvenation strategies. Control and NGPS MSCs were differentiated into bone in the presence or absence of sodium salicylate. Total RNA was extracted and global gene expression was analyzed.
2015-07-01 | E-GEOD-65172 | biostudies-arrayexpress