Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator‐activated receptors

Lee, T. I.; Kao, Yu Hsun; Chen, Y. C.; Chen, Y. J.

doi:10.1111/j.1365-2362.2008.02062.x

Cited by 23 publications

(25 citation statements)

References 36 publications

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“…In the present study, we also found that RGZ reversed the decrease in PPAR-α and PPAR-δ protein expression in hearts from diabetic SHRs and attenuated the increase in PPAR-γ mRNA and protein expression in hearts from diabetic SHRs. These results confirm further that oxidative stress and inflammation may play important roles in regulating cardiac PPAR isoforms and may explain why RGZ only decreased PPAR-γ expression in DM and hypertension complicated with DM, but not in HL-1 cells [14]. Furthermore, similar to previous studies, we found a lower BP in the RGZ-treated diabetic SHRs, which may also contribute to a decrease in inflammation and ROS in this group.…”

Section: Figure 2 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Protesupporting

confidence: 89%

“…* P < 0.05. and may enhance inflammation. Previous studies have shown that inflammation can regulate PPARs [7,14,[28][29][30]. In the present study, hypertension significantly increased pro-inflammatory cytokine expression and NADPH oxidase activity, and was even enhanced when complicated by DM.…”

Section: Figure 1 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Mrna mentioning

confidence: 44%

“…In addition, antioxidant treatment with ascorbic acid can reverse the changes in PPAR expression in diabetic rats [7], and atorvastatin also ameliorates the reduced expression of PPAR-α and PPAR-β/δ in cardiac hypertrophy [19]. Moreover, coenzyme Q10 reversed PPAR changes in TNF-α-treated cardiomyocytes [14], and resveratrol can attenuate the changes in PPAR expression in oxygen glucose deprivation-exposed neurons [33]. In the present study, we also found that RGZ reversed the decrease in PPAR-α and PPAR-δ protein expression in hearts from diabetic SHRs and attenuated the increase in PPAR-γ mRNA and protein expression in hearts from diabetic SHRs.…”

Section: Figure 2 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Protementioning

confidence: 94%

“…Our previous study has shown that TNF (tumour necrosis factor)-α regulates PPAR-α and PPAR-γ through oxidative stress in cardiomyocytes, suggesting inflammation has a potential effect on PPARs [14]. Studies on PPAR agonists have shown that they decrease inflammatory markers such as TNF-α and IL (interleukin)-1β in atherosclerotic lesions [15].…”

Section: Introductionmentioning

confidence: 98%

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Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes

et al. 2011

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Hypertension and DM (diabetes mellitus) are common chronic disorders that often co-exist. DM and PPAR (peroxisome-proliferator-activated receptor)-γ agonists may directly impair heart function. However, the effects of DM and PPAR-γ agonists on hypertensive myocardium are not known. Hence the aim of the present study was to investigate whether DM and a PPAR-γ agonist [RGZ (rosiglitazone)] modulated the effects of hypertension on myocardial expression of PPAR isoforms. Cardiac PPAR isoforms, TNF (tumour necrosis factor)-α and IL (interleukin)-6 were evaluated by real-time PCR and Western blotting in SHRs (spontaneously hypertensive rats), diabetic SHRs, diabetic SHRs treated with RGZ (5 mg/kg of body weight) and control WKY (Wistar-Kyoto) rats. Cardiac NADPH oxidase activity was quantified using a SOD (superoxide dismutase)-sensitive cytochrome c reduction assay. When compared with hearts from control WKY rats, hearts from SHRs had decreased PPAR-α and PPAR-δ mRNA and protein levels (39 and 44% respectively for PPAR-α, and 37 and 42% respectively for PPAR-δ), but had increased PPAR-γ mRNA and protein levels (1.9- and 1.4-fold respectively). The hypertension-induced changes in mRNA and protein of cardiac PPAR isoforms were enhanced in diabetic SHRs, which were attenuated in diabetic SHRs treated with RGZ. Cardiac TNF-α and IL-6 protein levels and NADPH oxidase activities were increased in SHRs and were increased further in diabetic SHRs. RGZ treatment decreased TNF-α and IL-6 protein levels and NADPH oxidase activities in hearts from diabetic SHRs. In conclusion, these findings suggest that DM and the PPAR-γ agonist modulated the hypertensive effects on cardiac PPAR isoform expression.

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Section: Figure 2 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Protesupporting

confidence: 89%

Section: Figure 1 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Mrna mentioning

confidence: 44%

Section: Figure 2 Cardiac Ppar-α (A) Ppar-γ (B) and Ppar-δ (C) Protementioning

confidence: 94%

Section: Introductionmentioning

confidence: 98%

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Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes

et al. 2011

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“…These results would explain why COX-2 levels were also reduced by pioglitazone after PPARg siRNA treatment. Other investigators have also found increased PPARg expression using rosiglitazone and pioglitazone [40,41] and suggest that the upregulated PPARg may contribute to the anti-inflammatory properties of glitazones and then contribute to the reduction of COX-2 expression.…”

Section: Discussionmentioning

confidence: 91%

Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress

Martin

Pérez-Girón

Hernanz

et al. 2012

Journal of Hypertension

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Interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by JAK2- and PI3K-induced STAT1/3 in HepG2 hepatocyte cells

et al. 2013

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Interleukin-6 (IL-6) is the major activator of the acute phase response (APR). One important regulator of IL-6-activated APR is peroxisome proliferator-activated receptor alpha (PPARα). Currently, there is a growing interest in determining the role of PPARα in regulating APR; however, studies on the molecular mechanisms and signaling pathways implicated in mediating the effects of IL-6 on the expression of PPARα are limited. We previously revealed that IL-6 inhibits PPARα gene expression through CAAT/enhancer-binding protein transcription factors in hepatocytes. In this study, we determined that STAT1/3 was the direct downstream molecules that mediated the Janus kinase 2 (JAK2) and phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways in IL-6-induced repression of PPARα. Treatment of cells with pharmacological inhibitors of JAK2, PI3K, AKT, and mTOR attenuated the inhibitory effect of IL-6 on PPARα protein in a dose-dependent manner. These inhibitors also decreased the IL-6-induced repression of PPARα mRNA expression and promoter activity. Overexpression of STAT1 and STAT3 in HepG2 cells cotransfected with a reporter vector containing this PPARα promoter region revealed that both the expression plasmids inhibited the IL-6-induced repression of PPARα promoter activity. In the presence of inhibitors of JAK2 and mTOR (AG490 and rapamycin, respectively), IL-6-regulated protein expression and DNA binding of STAT1 and STAT3 were either completely or partially inhibited simultaneously, and the IL-6-induced repression of PPARα protein and mRNA was also inhibited. This study has unraveled novel pathways by which IL-6 inhibits PPARα gene transcription, involving the modulation of JAK2/STAT1-3 and PI3K/AKT/mTOR by inducing the binding of STAT1 and STAT3 to STAT-binding sites on the PPARα promoter. Together, these findings represent a new model of IL-6-induced suppression of PPARα expression by inducing STAT1 and STAT3 phosphorylation and subsequent down-regulation of PPARα mRNA expression.

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Proinflammatory cytokine and ligands modulate cardiac peroxisome proliferator‐activated receptors

Abstract: Oxidative stress causes the regulations of PPAR-alpha and PPAR-gamma in the TNF-alpha-treated cardiomyocytes. The up-regulation of PPAR-gamma by PPAR ligands may contribute to their anti-inflammation effects.

Cited by 23 publications

References 36 publications

Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes

Cardiac peroxisome-proliferator-activated receptor expression in hypertension co-existing with diabetes

Peroxisome proliferator-activated receptor-γ activation reduces cyclooxygenase-2 expression in vascular smooth muscle cells from hypertensive rats by interfering with oxidative stress

Interleukin-6 inhibition of peroxisome proliferator-activated receptor alpha expression is mediated by JAK2- and PI3K-induced STAT1/3 in HepG2 hepatocyte cells

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