title: Grape pomace extract exerts antioxidant effects through an increase in GCS levels and GST activity in muscle and endothelial cells.
abstract: In a previous study, we demonstrated that a grape pomace extract (GPE) exerted antioxidant activity in endothelial (EA.hy926) and muscle (C2C12) cells through an increase in glutathione (GSH) levels. In the present study, in order to elucidate the mechanisms responsible for the antioxidant activity of GPE, its effects on the expression of critical antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD)1, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (GCS) were assessed in EA.hy926 and C2C12 cells. Moreover, the effects of GPE on CAT, SOD and glutathione S-transferase (GST) enzymatic activity were evaluated. For this purpose, the C2C12 and EA.hy926 cells were treated with GPE at low and non-cytotoxic concentrations (2.5 and 10 µg/ml for the C2C12 cells; 0.068 and 0.250 µg/ml for the EA.hy926 cells) for 3, 6, 12, 18 and 24 h. Following incubation, enzymatic expression and activity were assessed. The results revealed that treatment with GPE significantly increased GCS levels and GST activity in both the C2C12 and EA.hy926 cells. However, GPE significantly decreased CAT levels and activity, but only in the muscle cells, while it had no effect on CAT levels and activity in the endothelial cells. Moreover, treatment with GPE had no effect on HO-1 and SOD expression and activity in both cell lines. Therefore, the present results provide further evidence of the crucial role of GSH systems in the antioxidant effects exerted by GPE. Thus, GPE may prove to be effective for use as a food supplement for the treatment of oxidative stress-induced pathological conditions of the cardiovascular and skeletal muscle systems, particularly those associated with low GSH levels.
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Goutzourelas
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stagos
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Housmekeridou
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Karapouliou
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Efthalia
authors.initials: E
authors.lastname: Kerasioti
authors.affiliation: Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens 15771, Greece.
authors.forename: Nektarios
authors.initials: N
authors.lastname: Aligiannis
authors.affiliation: Division of Pharmacognosy and Natural Products Chemistry, School of Pharmacy, University of Athens, Athens 15771, Greece.
authors.forename: Alexios L
authors.initials: AL
authors.lastname: Skaltsounis
authors.affiliation: Laboratory of Clinical Virology, University of Crete, Medical School, Heraklion 71409, Greece.
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.affiliation: Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece.
authors.forename: Aristidis M
authors.initials: AM
authors.lastname: Tsatsakis
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece.
authors.forename: Demetrios
authors.initials: D
authors.lastname: Kouretas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D027843:Vitis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; C000606290:SOD1 protein, human; D002374:Catalase; D051547:Heme Oxygenase-1; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005982:Glutathione Transferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione