Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.
Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors.
Calò
Lorenzo A
LA
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padua, Padua 35100, Italy.
Zaghetto
Francesca
F
Pagnin
Elisa
E
Davis
Paul A
PA
De Mozzi
Paola
P
Sartorato
Paola
P
Martire
Giuseppe
G
Fiore
Cristina
C
Armanini
Decio
D
D000328:Adult; D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D002192:Canrenone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000097:blood*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009252:NADPH Dehydrogenase / Q000097:blood*; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
D026901:Membrane Transport Proteins; D000451:Mineralocorticoid Receptor Antagonists; D010750:Phosphoproteins; D017395:Plasminogen Activator Inhibitor 1; D000450:Aldosterone; D002192:Canrenone; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D006034:Glycyrrhetinic Acid