The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells.

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Inoue I, Goto S, Matsunaga T, Nakajima T, Awata T, Hokari S, Komoda T, Katayama S

Metabolism. 2001 Jan;50(1):3-11.

PubMed ID

11172467 [ View in PubMed

]

Abstract

We examined the effects of a variety of ligands/activators of the peroxisome proliferator-activated receptor (PPAR) on the expression of the superoxide scavenger enzyme, Cu2+,Zn2+-superoxide dismutase (CuZn-SOD), and the superoxide generating enzyme nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase in primary cultures of human umbilical vein endothelial cells (HUVEC) and human aorta endothelial cells (HAEC). Our data show that 3 types of PPARs, PPARalpha, PPARbeta/delta/Nuc1, and PPARgamma are expressed in endothelial cells. Bezafibrate, which is a ligand/activator for PPARalpha, increased the CuZn-SOD gene expression and protein levels in endothelial cells. Troglitazone and pioglitazone, which are ligands/activators for PPARgamma, also induced PPARalpha gene and protein expression and increased CuZn-SOD gene expression and protein levels in addition to increasing PPARgamma gene and protein expression in endothelial cells. Moreover, with treatment of monounsaturated and polyunsaturated fatty acids (PUFA), the CuZn-SOD mRNA levels were positively correlated with PPARalpha mRNA levels (r = .872, P < .0001) in primary endothelial cells. In addition, the phorbol myristate acetate (PMA)-stimulated or PMA-nonstimulated 22-kd a-subunit (p22phox) mRNA levels and 47-kd a-subunit (p47phox) protein levels in NADPH oxidase were decreased by treatment with PPARalpha and PPARgamma ligands/activators. These results suggest that PPARalpha and PPARgamma gene and protein expression in endothelial cells may play a physiologic role as radical scavengers, although the details of these mechanisms remain to be established.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bezafibrate	Peroxisome proliferator-activated receptor alpha	Protein	Humans	Yes	Agonist	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Arachidonic Acid	Experimental	PPARA	5465	upregulated	Arachidonic Acid results in increased expression of PPARA mRNA	22q13.31
Arachidonic Acid	Experimental	PPARD	5467	upregulated	Arachidonic Acid results in increased expression of PPARD mRNA	6p21.31
Arachidonic Acid	Experimental	PPARG	5468	downregulated	Arachidonic Acid results in decreased expression of PPARG mRNA	3p25.2
Bezafibrate	Approved Investigational	CYBA	1535	downregulated	Bezafibrate results in decreased expression of CYBA mRNA	16q24.2
Bezafibrate	Approved Investigational	PPARA	5465	upregulated	Bezafibrate results in increased expression of PPARA mRNA	22q13.31
Bezafibrate	Approved Investigational	PPARD	5467	upregulated	Bezafibrate results in increased expression of PPARD mRNA	6p21.31
Bezafibrate	Approved Investigational	SOD1	6647	upregulated	Bezafibrate results in increased expression of SOD1 mRNA	21q22.11
Icosapent	Approved Nutraceutical	CYBA	1535	downregulated	Eicosapentaenoic Acid results in decreased expression of CYBA mRNA	16q24.2
Icosapent	Approved Nutraceutical	PPARA	5465	upregulated	Eicosapentaenoic Acid results in increased expression of PPARA mRNA	22q13.31
Icosapent	Approved Nutraceutical	PPARD	5467	upregulated	Eicosapentaenoic Acid results in increased expression of PPARD mRNA	6p21.31
Icosapent	Approved Nutraceutical	PPARG	5468	upregulated	Eicosapentaenoic Acid results in increased expression of PPARG mRNA	3p25.2
Icosapent	Approved Nutraceutical	SOD1	6647	upregulated	Eicosapentaenoic Acid results in increased expression of SOD1 mRNA	21q22.11
Oleic Acid	Approved Investigational Vet Approved	PPARD	5467	upregulated	Oleic Acid results in increased expression of PPARD mRNA	6p21.31
Oleic Acid	Approved Investigational Vet Approved	PPARG	5468	upregulated	Oleic Acid results in increased expression of PPARG mRNA	3p25.2
Pioglitazone	Approved Investigational	CYBA	1535	downregulated	pioglitazone results in decreased expression of CYBA mRNA	16q24.2
Pioglitazone	Approved Investigational	PPARA	5465	upregulated	pioglitazone results in increased expression of PPARA mRNA	22q13.31
Pioglitazone	Approved Investigational	PPARG	5468	upregulated	pioglitazone results in increased expression of PPARG mRNA	3p25.2
Pioglitazone	Approved Investigational	SOD1	6647	upregulated	pioglitazone results in increased expression of SOD1 mRNA	21q22.11
Troglitazone	Approved Investigational Withdrawn	CYBA	1535	downregulated	troglitazone results in decreased expression of CYBA mRNA	16q24.2
Troglitazone	Approved Investigational Withdrawn	PPARA	5465	upregulated	troglitazone results in increased expression of PPARA mRNA	22q13.31
Troglitazone	Approved Investigational Withdrawn	PPARG	5468	upregulated	troglitazone results in increased expression of PPARG mRNA	3p25.2
Troglitazone	Approved Investigational Withdrawn	SOD1	6647	upregulated	troglitazone results in increased expression of SOD1 mRNA	21q22.11