H. Wang et Ja. Joseph, Structure-activity relationships of quercetin in antagonizing hydrogen peroxide-induced calcium dysregulation in PC12 cells, FREE RAD B, 27(5-6), 1999, pp. 683-694
Oxidative stress can induce neurotoxic insults by increasing intracellular
calcium (Ca2+), which has been implicated in various neurodegenerative dise
ases in aging. Previously, we showed that hydrogen peroxide induced calcium
dysregulation in PC12 cells, as evidenced by (i) an increase in calcium ba
selines, (ii) a decrease in depolarization-induced calcium influx, and (iii
) a failure to recover the Ca2+ levels. In the present experiments, we inve
stigated whether a dietary flavonoid, quercetin, can antagonize the effects
of hydrogen peroxide in the same cell model. We also investigated the poss
ible structure-activity relationships of quercetin by comparing the results
with four other flavonoids, each having a slightly different structure fro
m quercetin. Our results indicated that two structural components, includin
g (i) 3',4'-hydroxyl (OH) groups in the B ring and (ii) a 2,3-double bond i
n conjugation with a Core group in the C ring, along with the polyphenolic
structures were crucial for the protection. These structural components are
found in quercetin, and this compound was also the most efficacious in red
ucing both the H2O2-induced Ca2+ dysregulation in cells and oxidative stres
s assessed via the dichlorofluorescein assay. Collectively, these data indi
cated that the particular polyphenolic structural components of quercetin p
rovided its strong antioxidant property of protecting cells against H2O2-in
duced oxidative stress and calcium dysregulation. (C) 1999 Elsevier Science
Inc.