Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha (PPARα) in human hepatocarcinoma HepG2 cells by activation of NF-κB pathway

Lim, Wyi Sian; Ng, Di Lin; Kor, Sue Bee; Wong, Hong Kin; Muhammad, Tengku Sifzizul Tengku; Choo, Quok Cheong; Chew, Choy-Hoong

doi:10.1016/j.cyto.2012.10.007

Cited by 21 publications

(15 citation statements)

References 59 publications

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“…The use of inhibitors of the PPAR pathway or a method preventing its activation could enhance the advantage of using cancer immunotherapy based on V9V2 T cells. Indeed, the repression of PPAR expression can be induced by TNF [24] or by a group of N-(methylsulfonyl)amides derived from PPAR agonist carboxylic acids with an antagonist behavior on PPAR [25]. Some kinases or their activators can also lead to specific inhibition of PPAR transcriptional activity, such as the MEK1 or AMP-activated protein kinase activators 5-aminoimidazole-4-carboxamide riboside [26,27].…”

Section: Resultsmentioning

confidence: 99%

The PPARα pathway in Vγ9Vδ2 T cell anergy

Poupot

Boissard

Bétous

et al. 2014

Cellular and Molecular Biology Letters

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Phosphoantigens (PAgs) activate V9V2 T lymphocytes, inducing their potent and rapid response in vitro and in vivo. However, humans and nonhuman primates that receive repeated injections of PAgs progressively lose their V9V2 T cell response to them. To elucidate the molecular mechanisms of this in vivo desensitization, we analyzed the transcriptome of circulating V9V2 T cells from macaques injected with PAg. We showed that three PAg injections induced the activation of the PPAR pathway in V9V2 T cells. Thus, we analyzed the in vitro response of V9V2 T cells stimulated with a PPAR agonist. We demonstrated that in vitro PPAR pathway activation led to the inhibition of the BrHPP-induced activation and proliferation of human V9V2 T cells. Since the PPAR pathway is involved in the antigen-selective desensitization of human V9V2 T cells, the use of PPAR inhibitors could enhance cancer immunotherapy based on V9V2 T cells.

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Section: Resultsmentioning

confidence: 99%

The PPARα pathway in Vγ9Vδ2 T cell anergy

Poupot

Boissard

Bétous

et al. 2014

Cellular and Molecular Biology Letters

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“…These observations indicate that NF-κB and E2F1 are critical for hibernation. Since down regulation of PPARα depends on an intact signaling pathway of RELA [ 44 ] and E2F1 (an endogenous co-activator of NF-κB) [ 37 ], the potential of RELA and E2F1 to bind to the regulatory regions of Ppar α in non-hibernating bats suggests their roles in transcriptional repression of Ppar α. Similar binding preferences of FOXL1, NFYA, NFYB, SP1, TBP, ERG, RELA, and E2F1 on Ppar α were found in many other mammalian species (see Additional file 1 : Table S5 and Additional file 2 ).…”

Section: Resultsmentioning

confidence: 99%

Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in bats

et al. 2015

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BackgroundHibernation is a survival mechanism in the winter for some animals. Fat preserved instead of glucose produced is the primary fuel during winter hibernation of mammals. Many genes involved in lipid metabolism are regulated by the peroxisome proliferator-activated receptor alpha (PPARα). The role of PPARα in hibernation of mammals remains largely unknown. Using a multidisciplinary approach, we investigated whether PPARα is adapted to hibernation in bats.ResultsEvolutionary analyses revealed that the ω value of Pparα of the ancestral lineage of hibernating bats in both Yinpterochiroptera and Yangochiroptera was lower than that of non-hibernating bats in Yinpterochiroptera, suggesting that a higher selective pressure acts on Pparα in hibernating bats. PPARα expression was found to be increased at both mRNA and protein levels in distantly related bats (Rhinolophus ferrumequinum and Hipposideros armiger in Yinpterochiroptera and Myotis ricketti in Yangochiroptera) during their torpid episodes. Transcription factors such as FOXL1, NFYA, NFYB, SP1, TBP, and ERG were bioinformatically determined to have a higher binding affinity to the potential regulatory regions of Pparα in hibernating than in non-hibernating mammals. Genome-wide bioinformatic analyses of 64 mammalian species showed that PPARα has more potential target genes and higher binding affinity to these genes in hibernating than in non-hibernating mammals.ConclusionsWe conclude that PPARα is adapted to hibernation in bats based on the observations that Pparα has a more stringent functional constraint in the ancestral lineage of hibernating bats and a higher level of expression in hibernating than in non-hibernating bats. We also conclude that PPARα plays a very important role in hibernation as hibernators have more PPARα target genes than non-hibernators, and PPARα in hibernators has a higher binding affinity for its target genes than in non-hibernators.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0373-6) contains supplementary material, which is available to authorized users.

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“…One strategy used to block the NF-κB pathway is the pharmacological inhibition of IκB kinase (IKK). IKK is responsible for phosphorylating the inhibitory IκB protein, thereby releasing it from NF-κB, allowing for NF-κB activation [27]. VSMC were pre-treated with the IKK inhibitor wedelolactone (60 μM 1 h, Millipore) [27,28], incubated with H 2 O 2 , and investigated for ARPC2 expression.…”

Section: Resultsmentioning

confidence: 99%

“…IKK is responsible for phosphorylating the inhibitory IκB protein, thereby releasing it from NF-κB, allowing for NF-κB activation [27]. VSMC were pre-treated with the IKK inhibitor wedelolactone (60 μM 1 h, Millipore) [27,28], incubated with H 2 O 2 , and investigated for ARPC2 expression. Interestingly, our findings demonstrated that pharmacological inhibition of IKK does not inhibit H 2 O 2 -induced ARPC2 expression (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis Identifies an NADPH Oxidase 1 (Nox1)-Mediated Role for Actin-Related Protein 2/3 Complex Subunit 2 (ARPC2) in Promoting Smooth Muscle Cell Migration

Ghouleh

Rodríguez

Pagano

et al. 2013

IJMS

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A variety of vascular pathologies, including hypertension, restenosis and atherosclerosis, are characterized by vascular smooth muscle cell (VSMC) hypertrophy and migration. NADPH oxidase 1 (Nox1) plays a pivotal role in these phenotypes via distinct downstream signaling. However, the mediators differentiating these distinct phenotypes and their precise role in vascular disease are still not clear. The present study was designed to identify novel targets of VSMC Nox1 signaling using 2D Differential In-Gel Electrophoresis and Mass Spectrometry (2D-DIGE/MS). VSMC treatment with scrambled (Scrmb) or Nox1 siRNA and incubation with the oxidant hydrogen peroxide (H2O2; 50 μM, 3 h) followed by 2D-DIGE/MS on cell lysates identified 10 target proteins. Among these proteins, actin-related protein 2/3 complex subunit 2 (ARPC2) with no previous link to Nox isozymes, H2O2, or other reactive oxygen species (ROS), was identified and postulated to play an intermediary role in VSMC migration. Western blot confirmed that Nox1 mediates H2O2-induced ARPC2 expression in VSMC. Treatment with a p38 MAPK inhibitor (SB203580) resulted in reduced ARPC2 expression in H2O2-treated VSMC. Additionally, wound-healing “scratch” assay confirmed that H2O2 stimulates VSMC migration via Nox1. Importantly, gene silencing of ARPC2 suppressed H2O2-stimulated VSMC migration. These results demonstrate for the first time that Nox1-mediated VSMC migration involves ARPC2 as a downstream signaling target.

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Tumour necrosis factor alpha down-regulates the expression of peroxisome proliferator activated receptor alpha (PPARα) in human hepatocarcinoma HepG2 cells by activation of NF-κB pathway

Cited by 21 publications

References 59 publications

The PPARα pathway in Vγ9Vδ2 T cell anergy

The PPARα pathway in Vγ9Vδ2 T cell anergy

Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in bats

Proteomic Analysis Identifies an NADPH Oxidase 1 (Nox1)-Mediated Role for Actin-Related Protein 2/3 Complex Subunit 2 (ARPC2) in Promoting Smooth Muscle Cell Migration

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