Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear hormone receptor superfamily of transcription factors, widely expressed in the organism, including adipose, vascular and immune cells. Besides the well-known role in lipid/glycidic homeostasis, PPAR gamma has also recently emerged as a key regulator of inflammatory and immune responses. Besides the natural ligands, more potent synthetic agonists of PPAR gamma have been developed, including thiazolidinediones (TZDs), currently used in type 2 diabetes treatment, which also exert anti-inflammatory and anti-neoplastic effects. PPAR gamma mechanism of action has focused considerable attention over the years. This receptor was initially shown to act on gene expression through a direct transcription and an indirect transrepression activity, mainly associated with metabolic and anti-inflammatory effects. Different post-translational modifications of the receptor can modulate PPAR gamma activity. More recently, rapid nongenomic activity of TZDs affecting post-translation modifications of extranuclear proteins involved in cell signaling, has been reported. In particular, PPAR gamma can physically interact with protein kinases resulting in a compartment specific recruitment and activity modulation of these enzymes. Among them, ERK can be positively/negatively regulated by PPAR gamma ligands, as in endothelial cells, where TZDs exert anti-inflammatory effects through a novel mechanism involving a rapid inhibition of ERK1/2 phosphorylation/activation. Finally, some of the TZD anti-tumor effects seem to be PPAR gamma-independent, raising the possibility that alternative receptors can act through extranuclear nongenomic pathways.

Peroxisome proliferator-activated receptor gamma (PPARgamma): Is the genomic activity the only answer? / M. Luconi; G. Cantini; M. Serio. - In: STEROIDS. - ISSN 0039-128X. - STAMPA. - 75(2010), pp. 585-594. [10.1016/j.steroids.2009.10.012]

Peroxisome proliferator-activated receptor gamma (PPARgamma): Is the genomic activity the only answer?

LUCONI, MICHAELA;CANTINI, GIULIA;SERIO, MARIO
2010

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear hormone receptor superfamily of transcription factors, widely expressed in the organism, including adipose, vascular and immune cells. Besides the well-known role in lipid/glycidic homeostasis, PPAR gamma has also recently emerged as a key regulator of inflammatory and immune responses. Besides the natural ligands, more potent synthetic agonists of PPAR gamma have been developed, including thiazolidinediones (TZDs), currently used in type 2 diabetes treatment, which also exert anti-inflammatory and anti-neoplastic effects. PPAR gamma mechanism of action has focused considerable attention over the years. This receptor was initially shown to act on gene expression through a direct transcription and an indirect transrepression activity, mainly associated with metabolic and anti-inflammatory effects. Different post-translational modifications of the receptor can modulate PPAR gamma activity. More recently, rapid nongenomic activity of TZDs affecting post-translation modifications of extranuclear proteins involved in cell signaling, has been reported. In particular, PPAR gamma can physically interact with protein kinases resulting in a compartment specific recruitment and activity modulation of these enzymes. Among them, ERK can be positively/negatively regulated by PPAR gamma ligands, as in endothelial cells, where TZDs exert anti-inflammatory effects through a novel mechanism involving a rapid inhibition of ERK1/2 phosphorylation/activation. Finally, some of the TZD anti-tumor effects seem to be PPAR gamma-independent, raising the possibility that alternative receptors can act through extranuclear nongenomic pathways.
75
585
594
M. Luconi; G. Cantini; M. Serio
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/370897
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