Expression profiles of genes involved in the mouse nuclear factor-kappa B signal transduction pathway are modulated by mangiferin

Leiro, J.; Arranz, Juan A.; Yáñez, Matilde; Ubeira, Florencio M.; Sanmartín, M. L.; Orallo, Francisco

doi:10.1016/j.intimp.2004.03.002

Cited by 131 publications

(90 citation statements)

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“…Research is limited in the study of TNF on monocytes, that is, not much is known about the regulation of monocyte responses to TNF beyond the initial acute and transient activation of signaling pathways (23,24). The present study aimed to address the long-term exposure of monocytes to TNF.…”

Section: Discussionmentioning

confidence: 99%

TNF Mediates the Sustained Activation of Nrf2 in Human Monocytes

Rushworth

Shah

MacEwan

2011

The Journal of Immunology

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Modulation of monocyte function is a critical factor in the resolution of inflammatory responses. This role is mediated mainly by the production of TNF-a. Investigations of the actions of TNF have mostly focused on acute activation of other cell types such as fibroblasts and endothelial cells. Less is known about the effects of TNF on monocytes themselves, and little is known about the regulation of cell responses to TNF beyond the activation of NF-?B. In this study, we investigated the regulation of NF-E2–related factor 2 (Nrf2) cyctoprotective responses to TNF in human monocytes. We found that in monocytes TNF induces sustained Nrf2 activation and Nrf2 cytoprotective gene induction in a TNFR1-dependent manner. Under TNF activation, monocytes increased their expression of Nrf2-dependent genes, including NAD(P)H:quinone oxidoreductase 1 and glutamyl cysteine ligase modulatory, but not heme oxygenase-1. We also showed that autocrine TNF secretion was responsible for this sustained Nrf2 response and that Nrf2 activation by TNF was mediated by the generation of reactive oxygen species. Moreover, we showed that Nrf2-mediated gene induction can modulate TNF-induced NF-?B activation. These results show for the first time, to our knowledge, that TNF modulates prolonged Nrf2-induced gene expression, which in turn regulates TNF-induced inflammatory responses

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Section: Discussionmentioning

confidence: 99%

TNF Mediates the Sustained Activation of Nrf2 in Human Monocytes

Rushworth

Shah

MacEwan

2011

The Journal of Immunology

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“…First, MGR probably has direct effect on mitochondrial calcium uptake transporter activity, as has been reported for several other flavonoids (Montero et al, 2004). Second, MGR might affect mitochondrial calcium transporter expression, since evidence showed that MGR has the capability to modulate certain gene expressions (Leiro et al, 2004). These hypotheses require further investigation.…”

Section: Discussionmentioning

confidence: 77%

Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation

Agustini¹,

Arozal

Louisa

et al. 2015

Pharmaceutical Biology

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Context: The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves overproduction of free radicals that leads to intracellular calcium dysregulation and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has antioxidant and cardioprotective properties. However, its cardioprotection mechanism has yet to be revealed. Objective: This study determines whether the cardioprotective effect of MGR is caused by its effect on intracellular calcium regulation. Materials and methods: Male Sprague-Dawley rats were induced by DOX intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters examined were mRNA expression levels of proinflammatory cytokine gene (TNF-a), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and caspase-12), as well as cytosolic and mitochondrial calcium levels. Results: Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression levels of TNF-a by 44.55% and caspase-9 by 52.79%, as well as the cytosolic calcium level by 24.15% (p50.05). SERCA2a and caspase-12 expressions were only slightly affected (27.27% increase and 24.85% decrease for SERCA2a and caspase-12, respectively, p40.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant results in all parameters. Discussion and conclusion: MGR protected against DOX-induced cardiac inflammation and apoptosis via down-regulation of proapoptotic and proinflammatory gene expressions, upregulation of SERCA2a gene expression, and normalization of cytosolic calcium level. Thus, the cardioprotective effect of MGR is at least in part due to the regulation of intracellular calcium homeostasis. ARTICLE HISTORY

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“…The result was supported by previous studies showing that mangiferin exhibits anti-inflammatory effects, scavenges free radicals, and reduces oxidative stress. [21][22][23][24] Mangiferin also rescues neurons from cell death in acute injury and reduces neurological deficits caused by ischemic damage to the brain. 25) These findings suggest that scopolamine may cause cholinergic neuron injury and inflammation in the brain and that mangiferin may improve memory deficits by acetylcholine esterase inhibition or cholinergic receptor stimulation and inhibition of NF-kB activation.…”

Section: Mangiferin Increases Acetylcholine Level Reduced By Scopolammentioning

confidence: 99%