In vitro effects of reactive O2 species on the beta-receptor-adenylyl cyclase system.
The irreversible loss of activity of the sarcolemma-localized beta-receptor-adenylyl cyclase system (beta-RAS) in myocardial ischemia is a well documented phenomenon. Alterations in the sarcolemma (SL) induced by reactive O2 species could be responsible for this loss. Therefore the influence of oxidation of SH-groups and lipid peroxidation induced by Fe2+/Vit. C on the beta-RAS activity was studied. During incubation of SL with Fe2+/Vit. C a transient enhancement followed by a continuous loss of the beta-RAS activity (isoprenaline-, NaF-, Gpp(NH)p-, forskolin-stimulated and basal activity) was observed. In contrast there occurred a continuous loss of SH-groups and lipid peroxidation, beginning immediately after the start of incubation. Loss of SH-groups and lipid peroxidation as well as changes in the beta-RAS did not take place in the presence of the antioxidant t-Butyl-4-hydroxyanisole (BHA) or the Fe(2+)-chelator EGTA. In view of the known ischemia-induced formation of reactive O2 species our results show that these powerful oxidants could contribute to the modulation of the beta-RAS during myocardial ischemia.
Schimke
I
I
Institut für Pathologische und Klinische Biochemie, Humboldt-Universität zu Berlin, Germany.
Haberland
A
A
Will-Shahab
L
L
Küttner
I
I
Papies
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D005296:Ferrous Compounds / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000502:physiology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013552:Swine; D013858:Thiobarbiturates
D005296:Ferrous Compounds; D011943:Receptors, Adrenergic, beta; D013438:Sulfhydryl Compounds; D013858:Thiobarbiturates; C020748:ferrous sulfate; D000262:Adenylyl Cyclases; C029684:thiobarbituric acid; D001205:Ascorbic Acid; D010100:Oxygen