Singlet oxygen: a potential culprit in myocardial injury?
The purpose of this study was to explore the role of singlet oxygen in cardiovascular injury. To accomplish this objective, we investigated the effect of singlet oxygen [generated from photoactivation of rose-bengal] on the calcium transport and Ca(2+)-ATPase activity of cardiac sarcoplasmic reticulum and compared these results with those obtained by superoxide radical, hydrogen peroxide and hydroxyl radical. Isolated cardiac SR exposed to rose bengal (10 nM) irradiated at (560 nm) produced a significant inhibition of Ca2+ uptake; from 2.27 +/- 0.05 to 0.62 +/- 0.05 mumol Ca2+/mg.min (mean +/- SE) (P less than 0.01) and Ca(2+)-ATPase activity from 2.08 +/- 0.05 mumol Pi/min.mg to 0.28 +/- 0.04 mumol Pi/min.mg (mean +/- SE) (P less than 0.01). The inhibition of calcium uptake and Ca(2+)-ATPase activity by rose bengal derived activated oxygen (singlet oxygen) was dependent on the duration of exposure and intensity of light. The singlet oxygen scavengers ascorbic acid and histidine significantly protected SR Ca(2+)-ATPase against rose bengal derived activated oxygen species but superoxide dismutase and catalase did not attenuate the inhibition. SDS-polyacrylamide gel electrophoresis of SR exposed to photoactivated rose bengal up to 14 min, demonstrated complete loss of Ca(2+)-ATPase monomer band which was significantly protected by histidine. Irradiation of rose bengal also caused an 18% loss of total sulfhydryl groups of SR. On the other hand, superoxide (generated from xanthine oxidase action on xanthine) and hydroxyl radical (0.5 mM H2O2 + Fe(2+)-EDTA) as well as H2O2 (12 mM) were without any effect on the 97,000 dalton Ca(2+)-ATPase band of sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
Kukreja
R C
RC
Department of Medicine, Medical College of Virginia, Richmond 23298.
Jesse
R L
RL
Hess
M L
ML
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D004285:Dogs; D005609:Free Radicals / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides / Q000494:pharmacology; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology / Q000502:physiology*; D012395:Rose Bengal; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology
D000838:Anions; D005609:Free Radicals; D006878:Hydroxides; D013438:Sulfhydryl Compounds; D013481:Superoxides; D012395:Rose Bengal; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D000252:Calcium-Transporting ATPases; D010100:Oxygen; D002118:Calcium