15-deoxy-δ12,14-prostaglandin J2 induces apoptosis in human myofibroblasts by a pathway unrelated to peroxysome-proliferator-activated receptors, involving reactive oxygen species

Li, L.; Jia, Tao; Davaille, J.; Mallat, Ariane; Rieusset, Jennifer; Vidal, Hubert; Lotersztajn, Sophie

doi:10.1016/s0168-8278(01)81198-3

Cited by 11 publications

(16 citation statements)

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“…Here we have expanded the scope of result, but when we treated TrxR with PGs, 4-endogenous electrophiles examined to include HNE or 3,4-estrogen quinone, we found no LTA 4 , another arachidonic acid metabolite evidence of superoxide production in vitro (data produced by 5-lipoxygenase, and 3,4-EQ, a not shown). Consequently, we do not believe that metabolite produced by the hydroxylation and TrxRl is directly involved in PG-induced subsequent oxidatation of estrogen by cytochrome production of ROS (54,55). Consistent with our P450 (44).…”

Section: Fbs the Rko-ecr Cell Line Was Generated Bysupporting

confidence: 85%

Covalent Adducts Between Thioredoxin Reductase and Endogenous Electrophiles in Human Breast Cancer

Cassidy¹

2005

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Section: Fbs the Rko-ecr Cell Line Was Generated Bysupporting

confidence: 85%

Covalent Adducts Between Thioredoxin Reductase and Endogenous Electrophiles in Human Breast Cancer

Cassidy¹

2005

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“…On the other hand, the transition from activation to quiescence allows PPARγ to bind to MAT2A PPREs and inhibit transcriptional activity. It is known that RSG as well as other PPARγ agonists such as prostaglandin J2 have both PPARγ‐dependent and independent effects in cell types such as macrophages and hepatic myofibroblasts 26, 27. Therefore, to ascertain whether the effects of RSG on MAT2A were a consequence of PPARγ activity, we used the gene silencing and overexpression approach.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of methionine adenosyltransferase 2A by peroxisome proliferator-activated receptors in rat hepatic stellate cells

Ramani

Tomasi

2012

Hepatology

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Background and rationale Methionine adenosyltransferases (MAT) are critical enzymes that catalyze the formation of the methyl donor, S-adenosylmethionine (SAMe). The MAT2A gene, which encodes the catalytic subunit α2, is induced in de-differentiated liver. We previously demonstrated that MAT2A expression is enhanced in activated hepatic stellate cells (HSCs) and silencing this gene reduces HSC activation. In this study we examined the molecular mechanisms responsible for the transcriptional regulation of the MAT2A gene in HSCs. Results We identified peroxisome proliferator-activated receptor (PPAR) response elements (PPREs) in the rat MAT2A promoter. The PPARγ agonist, rosiglitazone (RSG) promoted quiescence in the activated rat HSC cell line (BSC) or culture-activated primary rat HSCs, decreased MAT2A expression and promoter activity and enhanced PPARγ binding to MAT2A PPREs. In vivo HSC activation in bile duct ligated (BDL) rats lowered PPARγ interaction with MAT2A PPREs. Silencing PPARγ increased MAT2A transcription whereas over-expressing it had the opposite effect demonstrating that PPARγ negatively controls this gene. Site-directed mutagenesis of PPREs abolished PPARγ recruitment to the MAT2A promoter and its inhibitory effect on MAT2A transcription in quiescent HSCs. PPRE mutations decreased the basal promoter activity of MAT2A in activated HSCs independent of PPARγ, indicating that other factors might be involved in PPRE interaction. We identified PPARβ binding to wild type but not to mutated PPREs, in activated cells. Furthermore, silencing PPARβ inhibited MAT2A expression and promoter activity. Forced expression of MAT2A in RSG-treated HSCs lowered PPARγ and enhanced PPARβ expression, thereby promoting an activated phenotype. Conclusion We have identified PPARγ as a negative regulator of MAT2A in quiescent HSCs. A switch from quiescence to activation state abolishes this control and allows PPARβ to up-regulate MAT2A transcription.

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“…Ciglitazone and rosiglitazone were found to cause mitochondrial depolarization and increase the steady-state ROS levels in glioma C6 cells and primary astrocytes. Recently, many studies have shown that cyclopentanone prostaglandins, such as 15-deoxy-⌬12,14-prostaglandin J 2 , an endogenous PPAR␥ ligand, induce intracellular stress through generation of ROS, and this may be the mechanism underlying its antiproliferative and antitumor effects (18,19,44). In this context, POX may be one of the mediators of PPAR␥ ligand-induced apoptosis through the production of ROS.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from their antidiabetic activity, glitazones have potent anti-inflammatory effects and are of special interest, since they induce growth arrest and apoptosis in a broad spectrum of tumor cells (15,16). PPAR␥ and its ligands have also been reported to induce intracellular oxidative stress, resulting in generation of reactive oxygen species (ROS) (17)(18)(19). Since the glitazones cause mitochondrial depolarization, the mitochondria are reported to be the most likely source of ROS, which have been implicated in mediating PPAR␥ ligand-induced growth arrest and apoptosis.…”

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confidence: 99%

Proline Oxidase, a Proapoptotic Gene, Is Induced by Troglitazone

Pandhare

Cooper

Phang

2006

Journal of Biological Chemistry

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Proline oxidase (POX) is a redox enzyme localized in the mitochondrial inner membrane. We and others have shown that POX is a p53-induced gene that can mediate apoptosis through generation of reactive oxygen species (ROS). The peroxisome proliferator-activated receptor ␥ (PPAR␥) ligand troglitazone was found to activate the POX promoter in colon cancer cells. PPAR␥ ligands have been reported to induce apoptosis in a variety of cancer cells. In HCT116 cells expressing a wild-type PPAR␥, troglitazone enhanced the binding of PPAR␥ to PPAR-responsive element in the POX promoter and increased endogenous POX expression. Blocking of PPAR␥ activation either by antagonist GW9662 or deletion of PPAR-responsive element in the POX promoter only partially decreased the POX promoter activation in response to troglitazone, indicating also the involvement of PPAR␥-independent mechanisms. Further, troglitazone also induced p53 protein expression in HCT116 cells, which may be the possible mechanism for PPAR␥-independent POX activation, since POX has been shown to be a downstream mediator in p53-induced apoptosis. In HCT15 cells, with both mutant p53 and mutant PPAR␥, there was no effect of troglitazone on POX activation, whereas in HT29 cells, with a mutant p53 and wild type PPAR␥, increased activation was observed by ligand stimulation, indicating that both PPAR␥-dependent and -independent mechanisms are involved in the troglitazone-induced POX expression. A time-and dose-dependent increase in POX catalytic activity was obtained in HCT116 cells treated with troglitazone with a concomitant increase in the production of intracellular ROS. Our results suggest that the induction of apoptosis by troglitazone may, at least in part, be mediated by targeting POX gene expression for generation of ROS by POX both by PPAR␥-dependent and -independent mechanisms.

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15-deoxy-δ12,14-prostaglandin J2 induces apoptosis in human myofibroblasts by a pathway unrelated to peroxysome-proliferator-activated receptors, involving reactive oxygen species

Cited by 11 publications

References 0 publications

Covalent Adducts Between Thioredoxin Reductase and Endogenous Electrophiles in Human Breast Cancer

Covalent Adducts Between Thioredoxin Reductase and Endogenous Electrophiles in Human Breast Cancer

Transcriptional regulation of methionine adenosyltransferase 2A by peroxisome proliferator-activated receptors in rat hepatic stellate cells

Proline Oxidase, a Proapoptotic Gene, Is Induced by Troglitazone

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