Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 26
Antioxidative effects of plant polyphenols: from protection of G-protein signaling to
prevention of age-related diseases
Viktor Jefremov1,2, Mihkel Zilmer1, Kersti Zilmer1, Nenad Bogdanovic3 and Ello
Karelson1
1Department of Biochemistry, Tartu University, 50411 Tartu, Estonia. E-mail:
ello.karelson@ut.ee; mihkel.zilmer@ut.ee; 2Department of Neurology and
Neurosurgery, Tartu University Hospital, 50411 Tartu, Estonia. E-mail:
viktor.jefremov@kliinikum.ee 3Geriatric Department, Neurotec, Karolinska Institute,
Karolinska University Hospital, S-14186 Huddinge, Stockholm, Sweden. E-mail:
nenad.bogdanovic@neurotec.ki.se
The oxidative stress hypothesis of aging and age-related diseases suggests beneficial effects
of antioxidative plant polyphenols in preventing and suppressing the neurodegeneration and
atherogenesis. Recent data reported that certain plant polyphenols, incl. phytoestrogens, can
improve cognitive function in aging and in Alzheimer’s disease (AD) and slow
atherosclerosis development (Joseph et al., 2005; Manach et al., 2005). However, the
mechanisms behind these protective actions of polyphenols remain to be elucidated. This
study was undertaken to elucidate the antioxidant potency of three polyphenols (resveratrol,
curcumin, genistein) by using the two human models: 1) down-regulation of pro-oxidant
stimulated G-proteins in the postmortem brain membranes of aging and AD subjects; 2)
elevation of oxy-resistance (lag-phase) of low-density lipoproteins (LDL) in the human
serum. We used [35S]-GTP$S binding to investigate the effects of polyphenols on the activity
of the stimulated G-proteins in the human brain membranes (Mahlapuu et al., 2003). The
effect of the agents on duration of lag-phase and maximal rate of the Cu2+-induced LDL
oxidation was determined by formation of conjugated dienes at 234 nm. In aging and AD
frontocortical (FC) membranes, 3-10 µM of investigated polyphenols dose-dependently
depressed the G-protein stimulation induced by 10 µM hydrogen peroxide or 500 µM
homocysteine (an approximate 25% stimulation by both pro-oxidants was observed). In aging
FC, resveratrol revealed higher antioxidant effects towards the stimulated G-proteins than
genistein whereas the effect of curcumin was lowest. In AD, the antioxidant potency for
curcumin showed significant decline from the value in normal aging whereas the antioxidant
effects for resveratrol and genistein did not reduce remarkably. In both, aging and AD brain
FC, the antioxidant effect of 3-10 µM 17-#-estradiol on the stimulated G-proteins showed
moderate values, similarly to genistein.
In the plasma concentration (1 µM), resveratrol, curcumin and genistein significantly
increased the resistance of LDL to oxidation, prolonging the oxidation lag-phase 4.5, 2.8 and
1.5 fold, respectively. The ability of curcumin and genistein to significantly reduce the
maximal rate of LDL oxidation (compared with control) might represent as a specific
mechanism enabling the moderate antioxidant (antiatherogenic) activity for these compounds.
Our results suggest that plant polyphenols have structure-dependent antioxidant
(antiatherogenic) potency which might realize via protection of G-proteins from oxidative
damage in normal aging and neurodegeneration as well as via prevention of LDL from
abnormal (excessive) oxidation in atherogenesis.
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