Peroxisome Proliferator-Activated Receptors and Shock State

Esposito, Emanuela; Cuzzocrea, Salvatore; Meli, Rosaria

doi:10.1100/tsw.2006.298

Cited by 8 publications

(6 citation statements)

References 121 publications

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“…Moreover, we also demonstrated that GW0742 inhibited NF-B translocation. Taken together, the balance between proinflammatory and prosurvival roles of NF-B may depend on the phosphorylation status of p65, and PPAR-␤/␦ may play a central role in this process (Esposito et al, 2006;Glass and Ogawa, 2006;Straus and Glass, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Both PPAR-␣ and PPAR-␥ have been well characterized for their roles in lipid and glucose metabolism by using specific marketed drugs such as the thiazolidinediones, ligands of PPAR-␥ prescribed for the treatment of type-2 diabetes (Rodríguez-Calvo et al, 2008); and the fibrates, PPAR-␣ ligands prescribed for their lipid-modulating properties (Ricote et al, 2004). PPARs have been implicated in the pathogenesis several diseases, including diabetes mellitus, obesity, atherosclerosis, neurological diseases, and SCI (Esposito et al, 2006;Di Paola and Cuzzocrea, 2007); therefore, they represent an important pharmacological target.…”

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confidence: 99%

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Evidence for the Role of Peroxisome Proliferator-Activated Receptor-β/δ in the Development of Spinal Cord Injury

Paterniti

Esposito²,

Mazzon

et al. 2010

J Pharmacol Exp Ther

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Several lines of evidence suggest a biological role for peroxisome proliferator-activated receptor (PPAR)-␤/␦ in the pathogenesis many diseases. The aim of the present study was to evaluate the contribution of PPAR-␤/␦ in the secondary damage in experimental spinal cord injury (SCI) in mice. To this purpose, we used 4- [[[2-[3-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742), a high-affinity PPAR-␤/␦ agonist. Spinal cord trauma was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T 5 to T 8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of inflammatory mediators, tissue damage, and apoptosis. GW0742 treatment (0.3 mg kg Ϫ1 i.p.) 1 and 6 h after the SCI significantly reduced 1) the degree of spinal cord inflammation and tissue injury (histological score), 2) neutrophil infiltration (myeloperoxidase activity), 3) nitrotyrosine formation, 4) proinflammatory cytokines expression, 5) nuclear factor-B activation, 6) inducible nitric-oxide synthase expression, and 6) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, FasL, Bax, and Bcl-2 expression). Moreover, GW0742 significantly ameliorated the recovery of limb function (evaluated by motor recovery score). To elucidate whether the protective effects of GW0742 are related to activation of the PPAR-␤/␦ receptor, we also investigated the effect of PPAR-␤/␦ antagonist methyl 3-({[2-(methoxy)-4 phenyl]amino}sulfonyl)-2-thiophenecarboxylate (GSK0660) on the protective effects of GW0742. GSK0660 (1 mg/kg i.p. 30 min before treatment with GW0742) significantly blocked the effect of the PPAR-␤/␦ agonist and thus abolished the protective effect. Our results clearly demonstrate that GW0742 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.Spinal cord injury (SCI) is a highly debilitating pathology. Although innovative medical care has improved patient outcome, advances in pharmacotherapy for the purpose of limiting neuronal injury and promoting regeneration have been limited. The complex pathophysiology of SCI may explain the difficulty in finding a suitable therapy. The primary traumatic mechanical injury to the spinal cord causes the death of many neurons that cannot be recovered and regenerated.Studies indicate that neurons continue to die for hours after traumatic SCI (Profyris et al., 2004). The events that characterize this successive phase to mechanical injury are called "secondary damage." The secondary damage is determined by a large number of cellular, molecular, and biochemical cascades. Recent data suggest the presence of a local inflammatory response, which amplifies the secondary damage. The cardinal features of inflammation, namely, infiltration of inflammatory cells (polymorphonuclear neutrophils, macrophages and lymphocytes); release of inflammatory mediators; and activation of endothelial cells leading to increa...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Evidence for the Role of Peroxisome Proliferator-Activated Receptor-β/δ in the Development of Spinal Cord Injury

Paterniti

Esposito²,

Mazzon

et al. 2010

J Pharmacol Exp Ther

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“…ChREBP is a transcription factor that recognizes the carbohydrate response element (ChRE) in glycolysis and lipid synthesis gene promoter [37, 38]. The peroxisome proliferator-activated receptors (PPARs), transcription factors that regulate lipid metabolism and insulin sensitivity [39], consist of three isoforms: PPAR γ , PPAR α , and PPAR δ [40]. PPAR γ is highly expressed in adipocytes while it is also present in other hepatocytes, especially in resting HSCs [41].…”

Section: Crosstalk Between Hepatocytes Hepatic Nonparenchymal Celmentioning

confidence: 99%

The Crosstalk between Fat Homeostasis and Liver Regional Immunity in NAFLD

Duan

Zhong

et al. 2019

Journal of Immunology Research

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The liver is well known as the center of glucose and lipid metabolism in the human body. It also functions as an immune organ. Previous studies have suggested that liver nonparenchymal cells are crucial in the progression of NAFLD. In recent years, NAFLD's threat to human health has been becoming a global issue. And by far, there is no effective treatment for NAFLD. Liver nonparenchymal cells are stimulated by lipid antigens, adipokines, or other factors, and secreted immune factors can alter the expression of key proteins such as SREBP-1c, ChREBP, and PPARγ to regulate lipid metabolism, thus affecting the pathological process of NAFLD. Interestingly, some ncRNAs (including miRNAs and lncRNAs) participate in the pathological process of NAFLD by changing body fat homeostasis. And even some ncRNAs could regulate the activity of HSCs, thereby affecting the progression of inflammation and fibrosis in the course of NAFLD. In conclusion, immunotherapy could be an effective way to treat NAFLD.

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“… 5 PPARs are involved in the pathogenesis of several diseases, including diabetes mellitus, obesity, atherosclerosis, neurological diseases, and SCI. 6 – 8 It has been documented that GW0742 (a selective agonist of PPARδ) can reduce the development of inflammation and tissue injury associated with SCI. 9 However, application of useful medication in patients with SCI is still not enough.…”

Section: Introductionmentioning

confidence: 99%

Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

Lin

Tsai

Chang

et al. 2015

DDDT

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BackgroundDecrease of peroxisome proliferator-activated receptors-δ (PPARδ) expression has been observed after spinal cord injury (SCI). Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.MethodsIn the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.ResultsRecovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.ConclusionThe obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.

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Peroxisome Proliferator-Activated Receptors and Shock State

Cited by 8 publications

References 121 publications

Evidence for the Role of Peroxisome Proliferator-Activated Receptor-β/δ in the Development of Spinal Cord Injury

Evidence for the Role of Peroxisome Proliferator-Activated Receptor-β/δ in the Development of Spinal Cord Injury

The Crosstalk between Fat Homeostasis and Liver Regional Immunity in NAFLD

Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

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