Modulating effect of flavonoids and their derivatives on sarcoplasmic reticulum Ca2+-ATPase oxidized by hypochloric acid and peroxynitrite.
OBJECTIVE
Effect of rutin and its lipophilic derivatives on Ca2+-ATPase of sarcoplasmic reticulum (SERCA) oxidized by hypochloric acid and peroxynitrite was investigated to examine the role of flavonoids in SERCA activity modulation.


METHODS
Ca2+-ATPase activity was measured spectrophotometrically at 37 degrees C using NADH-coupled enzyme pyruvate kinase/lactate dehydrogenase assay. SERCA was oxidized by HOCl (3 min) or ONOO- (30 s) after previous treatment with flavonoids (2 min) at 37 degrees C. Lipophilic rutin derivatives were prepared by lipase-catalyzed esterification of flavonoids with fatty acids.


RESULTS
Both hypochloric acid (HOCl) and peroxynitrite (ONOO-) decreased ATPase activity concentration-dependently with IC50 of 50+/-10 micromol/l and 150+/-15 micromol/l, respectively. Rutin was found to have a protective effect on SERCA activity in both oxidation systems in the concentration range 5 - 250 micromol/l. Lipophilic rutin derivatives (rutin oleate, rutin linoleate, rutin linolenate) exerted inhibitory effect on ATPase activity both in the presence and absence of oxidants.


CONCLUSIONS
The results suggest that selective lipophilization of the flavonoid skeleton may represent a useful tool for SERCA activity modulation.
Viskupicova
Jana
J
Department of Nutrition and Food Assessment, Slovak University of Technology, Slovakia. janaviskupicova@gmail.com
Strosova
Miriam
M
Sturdik
Ernest
E
Horakova
Lubica
L
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006997:Hypochlorous Acid / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000737:chemistry*; D011770:Pyruvate Kinase / Q000378:metabolism; D011817:Rabbits; D012431:Rutin / Q000031:analogs & derivatives / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D013053:Spectrophotometry
D000975:Antioxidants; D005419:Flavonoids; D016877:Oxidants; D030421:Peroxynitrous Acid; D012431:Rutin; D006997:Hypochlorous Acid; D007770:L-Lactate Dehydrogenase; D011770:Pyruvate Kinase; D000252:Calcium-Transporting ATPases