Heme oxygenase induction by UVA radiation. A response to oxidative stress in rat liver.
Heme oxygenase is a key enzyme for heme catabolism and catalyzes the oxidative degradation of heme to form biliverdin IX alpha, an immediate precursor of bilirubin. In order to shed light on the mechanism by which UVA radiation causes oxidative damage, the relationship between heme oxygenase induction and oxidative stress was studied. HO-1 activity, lipid peroxidation and generation of active oxygen species (H2O2) were measured in rat liver exposed to UVA radiation. Besides, soluble and enzymatic antioxidant defenses (GSH, SOD, CAT and GSH-Px) were determined, while bilirubin antioxidant capacity was also evaluated. UVA radiation markedly increased both lipid peroxidation (180% +/- 7; S.E.M., n = 9 over control value of 0.1 +/- 0.01 nmol MDA/min per mg prot.) and steady state concentration of hydrogen peroxide (4 +/- 0.03 microM; S.E.M., n = 9) 3 h after treatment. At the same time, GSH content decreased to 3.6 +/- 0.2 mumol/g liver (S.E.M., n = 9) increasing thereafter. Antioxidant enzymes reached minimum values 6 h after UVA treatment (SOD: 7.2 +/- 0.2 U/mg protein, CAT: 7.8 +/- 0.2 pmol/mg protein, GSH-Px: 0.088 +/- 0.004 U/mg protein; S.E.M., n = 9), starting to increase 12 h after irradiation. HO-1 induction was observed 6 h after UVA irradiation, reaching a maximum value of 2.5 +/- 0.03 U/mg protein (S.E.M., n = 9) 12 h after treatment, and then declined until it reached control levels 24 h after exposure. Administration of bilirubin 2 h before UVA irradiation, entirely prevented HO-1 induction, the increase in MDA content and the decrease in GSH levels. This study shows that UVA irradiation leads to oxidative stress as evidenced by increased MDA content and H2O2 steady state levels, and depletion of GSH, SOD, CAT and GSH-Px. All these changes produced HO-1 induction. It is concluded that the induction of this enzyme could be a response to oxidative stress, since bilirubin can act as a physiological antioxidant.
Ossola
J O
JO
Departamento de Química Biológica, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina.
Tomaro
M L
ML
D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D002374:Catalase / Q000032:analysis; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D004790:Enzyme Induction / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000528:radiation effects; D008099:Liver / Q000201:enzymology / Q000528:radiation effects*; D008315:Malondialdehyde / Q000032:analysis; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis; D014466:Ultraviolet Rays
D008315:Malondialdehyde; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D015500:Chloramphenicol O-Acetyltransferase; D005978:Glutathione; D001663:Bilirubin