Effect of glycyrrhetinic acid on membrane band 3 in human erythrocytes.
Glycyrrhetinic acid (GA) is a hydrolytic product of the triterpene glycoside of glycyrrhizic acid, one of the main constituents of licorice root, which has long been studied, due to its several biological and endocrine properties. In this paper, GA was tested on human erythrocytes, and GA-induced alterations were compared with those caused by diamide, a mild oxidant inducing well-characterized cell/membrane alterations, and n-ethylmaleimide (NEM), as alkylating agent. In order to verify the biochemical steps underlying the action of GA, band 3 Tyr-phosphorylation level, enzyme recruitment and band 3 clustering in cells pre-incubated with GA before diamide treatment were all examined. Results show that GA, in a dose-dependent manner, prevents both diamide and NEM-induced band 3 Tyr-phosphorylation, but not GSH decrease caused by both compounds. In addition, diamide-induced band 3 clustering and IgG binding to altered cells were also completely reversed by GA pre-treatment. Also, when membrane sensitivity toward proteolytic digestion was tested, GA-treated cells showed high resistance to proteolysis. In conclusion, in human erythrocytes, GA is proposed to strengthen membrane integrity against both oxidative and proteolytic damage.
Fiore
Cristina
C
Department of Medical and Surgical Sciences-Endocrinology University of Padua, Via Ospedale 105, Padova, Italy.
Bordin
Luciana
L
Pellati
Donatella
D
Armanini
Decio
D
Clari
Giulio
G
D000477:Alkylating Agents / Q000378:metabolism / Q000494:pharmacology; D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D003958:Diamide / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005033:Ethylmaleimide / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D019803:Glutathione Disulfide / Q000032:analysis; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D014443:Tyrosine / Q000378:metabolism
D000477:Alkylating Agents; D001457:Anion Exchange Protein 1, Erythrocyte; D000975:Antioxidants; D007074:Immunoglobulin G; D016877:Oxidants; D003958:Diamide; D014443:Tyrosine; D005978:Glutathione; D005033:Ethylmaleimide; D006034:Glycyrrhetinic Acid; D019803:Glutathione Disulfide