Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of PPAR-gamma activity

Zuo, Xiangsheng; Wu, Yuanqing; Morris, Jeffrey S.; Stimmel, Julie B.; Leesnitzer, Lisa M.; Fischer, Susan M.; Lippman, Scott M.; Shureiqi, Imad

doi:10.1038/sj.onc.1209160

Cited by 98 publications

(97 citation statements)

References 36 publications

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“…Actually, gemfibrozil inhibited the expression of PPAR-␥ in mixed glial cells. Recently it has been reported that PPAR-␤ may function to repress PPAR-␣ and PPAR-␥ target gene expression in certain type of cells (39). Similarly to the stimulation of PPAR-␤ in pure oligodendrocytes, gemfibrozil was also able to increase the level of PPAR-␤ in primary mixed glial cells and spinal cord organotypic cultures.…”

Section: Discussionmentioning

confidence: 77%

Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β

Jana

Mondal

Gonzalez

et al. 2012

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 77%

Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β

Jana

Mondal

Gonzalez

et al. 2012

Journal of Biological Chemistry

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“…A crossroad between PPARs was already suggested previously. PPAR␤/␦ activation by agonists or PPAR␤/␦ overexpression inhibits PPAR␥ (Shi et al, 2002;Zuo et al, 2006) and PPAR␣ activity (Shi et al, 2002) in both cancer and normal cells. It was also shown that the synthetic PPAR␤/␦ agonists increase PPAR␥-induced differentiation of adipocytes (Matsusue et al, 2004) or C6 glioma cells (Leisewitz et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor (PPAR)-γ Positively Controls and PPARα Negatively Controls Cyclooxygenase-2 Expression in Rat Brain Astrocytes through a Convergence on PPARβ/δ via Mutual Control of PPAR Expression Levels

Aleshin

Grabeklis²,

Hanck³

et al. 2009

Mol Pharmacol

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Peroxisome proliferator-activated receptor (PPAR) transcription factors are pharmaceutical drug targets for treating diabetes, atherosclerosis, and inflammatory degenerative diseases. The possible mechanism of interaction between the three PPAR isotypes (␣, ␤/␦, and ␥) is not yet clear. However, this is important both for understanding transcription factor regulation and for the development of new drugs. The present study was designed to compare the effects of combinations of synthetic agonists of PPAR␣ [2-[4-[2-[4-cyclohexylbutyl (cyclohexylcarbamoyl), and PPAR␥ (rosiglitazone, ciglitazone) on inflammatory gene regulation in rat primary astrocytes. We measured cyclooxygenase-2 (COX-2) expression and prostaglandin E 2 synthesis in lipopolysaccharide (LPS)-stimulated cells. PPAR␣, PPAR␤/␦, and PPAR␥ knockdown models served to delineate the contribution of each PPAR isotype. Thiazolidinediones enhanced the LPSinduced COX-2 expression via PPAR␥-dependent pathway, whereas L-165041 and GW7647 had no influence. However, the addition of L-165041 potentiated the effect of PPAR␥ activation through PPAR␤/␦-dependent mechanism. On the contrary, PPAR␣ activation (GW7647) suppressed the effect of the combined L-165041/rosiglitazone application. The mechanism of the interplay arising from combined applications of PPAR agonists involves changes in PPAR expression levels. A PPAR␤/␦ overexpression model confirmed that PPAR␤/␦ expression level is the point at which PPAR␥ and PPAR␣ pathways converge in control of COX-2 gene expression. Thus, we discovered that in primary astrocytes, PPAR␥ has a positive influence and PPAR␣ has a negative influence on PPAR␤/␦ expression and activity. A positive/negative-feedback loop is formed by PPAR␤/␦-dependent increase in PPAR␣ expression level. These findings elucidate a novel principle of regulation in the signaling by synthetic PPAR agonists that involves modulating the interaction between PPAR␣, -␤/␦, and -␥ isoforms on the level of their expression.

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“…Not I linkers were added and then ligated to generate plasmid pAC. A 578 base pair (bp) of hTERT promoter was excised from plasmid pAd/TERT 51 with Eco RI/Sal I, and filled in with Klenow large DNA fragment (Invitrogen). Hind III linkers were added and ligated to generate plasmid pACTERT.…”

Section: Methodsmentioning

confidence: 99%

Adenoviral mediated transduction of adenoid cystic carcinoma by human TRAIL gene driven with hTERT tumor specific promoter induces apoptosis

Zang¹,

Miao²,

Mu³

et al. 2009

Cancer Biology & Therapy

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Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of PPAR-gamma activity

Cited by 98 publications

References 36 publications

Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β

Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β

Peroxisome Proliferator-Activated Receptor (PPAR)-γ Positively Controls and PPARα Negatively Controls Cyclooxygenase-2 Expression in Rat Brain Astrocytes through a Convergence on PPARβ/δ via Mutual Control of PPAR Expression Levels

Adenoviral mediated transduction of adenoid cystic carcinoma by human TRAIL gene driven with hTERT tumor specific promoter induces apoptosis

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