Resveratrol Up-Regulates the Erythrocyte Plasma Membrane Redox System and Mitigates Oxidation-Induced Alterations in Erythrocytes During Aging in Humans
Restricted accessResearch articleFirst published online June, 2013
Resveratrol Up-Regulates the Erythrocyte Plasma Membrane Redox System and Mitigates Oxidation-Induced Alterations in Erythrocytes During Aging in Humans
Reactive oxygen/nitrogen species (ROS/RNS)–mediated oxidative damage followed by disturbed cellular homeostasis is involved in aging and related consequences. Lipid peroxidation, post-translational modifications of proteins, and an impaired defense system due to increased oxidative stress jeopardize cell fate and functions, resulting in cell senescence. Resveratrol, a natural stilbene, has extensively been reported to elicit a plethora of health-promoting effects. The present study carried out on 97 healthy human subjects (62 males and 35 females) of both sexes provides experimental evidence that resveratrol confers ability to up-regulate the plasma membrane redox system (PMRS) along with ascorbate free radical reductase, a compensatory system operating in the cell to maintain cellular redox state. Furthermore, resveratrol provided significant protection against lipid peroxidation and protein carbonylation and restored the cellular redox homeostasis measured in terms of glutathione (GSH) and sulfhydryl (–SH) group levels during oxidation injury in erythrocytes of different age groups in humans. Findings suggest a possible role of resveratrol in retardation of age-dependent oxidative stress.
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References
1.
HarmanD. Free radical theory of aging: An update. Ann NY Acad Sci, 2006; 1067:1–12.
2.
MonaghanP, MetcalfeNB, TorresR. Oxidative stress as a mediator of life history trade-offs: Mechanisms, measurements and interpretation. Ecol Lett, 2009; 12:75–92.
3.
DrogeW. Free radicals in the physiological control of cell function. Physiol Rev, 2002; 82:47–95.
4.
HalliwellB, GutteridgeJMC. Cellular responses to oxidative stress: Adaptation, damage, repair, senescence and death. Free Radicals in Biology and Medicine, 4th. Oxford University Press: New York, 2007; 187–267.
5.
RadakZ, ZhaoZ, GotoS, KoltaiE. Age-associated neurodegeneration and oxidative damage to lipids, proteins and DNA. Mol Aspects Med, 2011; 32:305–315.
6.
HawkinsCL, MorganPE, DaviesMJ. Quantification of protein modification by oxidants. Free Radic Biol Med, 2009; 46:965–988.
7.
PandeyKB, RizviSI. Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid Med Cell Longev, 2010; 3:2–12.
8.
BallatoriN, KranceSM, NotenboomS, ShiS, TieuK, HammondCL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem, 2009; 390:191–214.
9.
QueenBL, TollefsbolTO. Polyphenols and aging. Curr Aging Sci, 2010; 3:34–42.
10.
CsiszarA. Anti-inflammatory effects of resveratrol: Possible role in prevention of age-related cardiovascular disease. Ann NY Acad Sci, 2011; 1215:117–122.
11.
TimmersS, AuwerxJ, SchrauwenP. The journey of resveratrol from yeast to human. Aging (Albany NY), 2012; 4:146–158.
12.
PandeyKB, JhaR, RizviSI. Erythrocyte membrane transporters during human ageing: Modulatory role of tea catechins. Clin Exp Pharmacol Physiol, 2013; 40:83–89.
13.
VanDuijnMM, TijssenK, Van SteveninckJ, Van Den BroekPJ, Van Der ZeeJ. Erythrocytes reduce extracellular ascorbate free radicals using intracellular ascorbate as an electron donor. J Biol Chem, 2000; 275:27720–27725.
14.
RizviSI, JhaR, MauryaPK. Erythrocyte plasma membrane redox system in human aging. Rejuvenation Res, 2006; 9:470–474.
15.
de GreyADNJ. The plasma membrane redox system: A candidate source of aging-related oxidative stress. AGE, 2005; 27:129–138.
16.
RizviSI, PandeyKB, JhaR, MauryaPK. Ascorbate recycling by erythrocytes during aging in humans. Rejuvenation Res, 2009; 12:3–6.
17.
RizviSI, PandeyKB. Activation of the erythrocyte plasma membrane redox system by resveratrol: A possible mechanism for antioxidant properties. Pharmacol Rep, 2010; 62:726–732.
18.
PandeyKB, RizviSI. Protective effect of resveratrol on formation of membrane protein carbonyls and lipid peroxidation in erythrocytes subjected to oxidative stress. Appl Physiol Nutr Metab, 2009; 34:1093–1097.
19.
LowryOH, RosebroughNJ, FarrAL, RandallRJ. Protein measurement with the Folin phenol reagent. J Biol Chem, 1951; 193:265–275.
20.
MayJM, QuZC, CobbCE. Human erythrocyte recycling of ascorbic acid: Relative contributions from the ascorbate free radical and dehydroascorbic acid. J Biol Chem, 2004; 279:14975–14982.
21.
EsterbauerH, CheesemanKH. Determination of aldehydic lipid peroxidation products: Malondialdehyde and 4-hydroxynonenal. Methods Enzymol, 1990; 186:407–413.
22.
PandeyKB, RizviSI. Protective effect of resveratrol on markers of oxidative stress in human erythrocytes subjected to in vitro oxidative insult. Phytother Res, 2010; 24:S11–S14.
23.
LevineRL, GarlandD, OliverCN, AmiciA, ClimentI, LenzAGet al.Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol, 1990; 186:464–479.
24.
KitajimaH, AmaguchiT, KinotoE. Hemolysis of human erythrocytes under hydrostatic pressure is suppressed by cross-linking of membrane proteins. J Biochem, 1990; 108:1057–1062.
25.
HyunDH, KimJ, MoonC, LimCL, de CaboR, MattsonMP. The plasma membrane redox enzyme NQO1 sustains cellular energetics and protects human neuroblastoma cells against metabolic and proteotoxic stress. AGE, 2012; 34:359–370.
26.
De LucaT, MorreDM, ZhaoH, MorreDJ. NAD+/NADH and/or CoQ/CoQH2 ratios from plasma membrane electron transport may determine ceramide and sphingosine-1-phosphate levels accompanying G1 arrest and apoptosis. Biofactors, 2005; 25:43–60.
27.
AdlardPA, BushAI. The plasma membrane redox system in Alzheimer's disease. Exp Neurol., 2011; 228:9–14.
28.
HarrisonFE, MayJM. Vitamin C function in the brain: Vital role of the ascorbate transporter SVCT2. Free Radic Biol Med, 2009; 46:719–730.
29.
HemilaH, KaprioJ. Modification of the effect of vitamin E supplementation on the mortality of male smokers by age and dietary vitamin C. Am J Epidemiol, 2009; 169:946–953.
30.
PandeyKB, RizviSI. Upregulation of erythrocyte ascorbate free radical reductase by tea catechins: Correlation with their antioxidant properties. Food Res Int, 2012; 46:46–49.
31.
NishikimiM, FukuyamaR, MinoshimaS, ShimizuN, YagiK. Cloning and chromosomal mapping of the human nonfunctional gene for L-gulonogamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J Biol Chem, 1994; 269:13685–13688.
32.
Fernández-MarMI, MateosR, García-ParrillaMC, PuertasB, Cantos-VillarE. Bioactive compounds in wine: Resveratrol, hydroxytyrosol and melatonin: A review. Food Chem, 2012; 130:797–813.
33.
HyunDH, EmersonSS, JoDG, MattsonMP, de CaboR. Calorie restriction upregulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci USA, 2006; 103:19908–19912.
34.
LongJ, LiuC, SunL, GaoH, LiuJ. Neuronal mitochondrial toxicity of malondialdehyde: Inhibitory effects on respiratory function and enzyme activities in rat brain mitochondria. Neurochem Res, 2009; 34:786–794
35.
NikiE. Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products?FEBS Lett, 2012; 586:3767–3770.
36.
StadtmanER. Protein oxidation and aging. Free Radic Res, 2006; 40:1250–1258.
37.
LevineRL, StadtmanER. Oxidative modification of proteins during aging. Exp Gerontol, 2001; 36:1495–1502.
38.
PonizovskyAM, BarshteinG, BergelsonLD. Biochemical alterations of erythrocytes as an indicator of mental disorders: An overview. Harv Rev Psychiatry, 2003; 11:317–332.
39.
FernándezAF, FragaMF. The effects of the dietary polyphenol resveratrol on human healthy aging and lifespan. Epigenetics, 2011; 6:870–874.
40.
NakamuraA, KawakamiK, KametaniF, NakamotoH, GotoS. Biological significance of protein modifications in aging and calorie restriction. Ann NY Acad Sci, 2010; 1197:33–39.
41.
CroweE, SellC, ThomasJD, JohannesGJ, TorresC. Activation of proteasome by insulin-like growth factor-I may enhance clearance of oxidized proteins in the brain. Mech Ageing Dev, 2009; 130:793–800.
42.
ZhuY, CarveyPM, LingZ. Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res, 2006; 1090:35–44.
43.
WangX, WuZ, SongG, WangH, LongM, CaiS. Effects of oxidative damage of membrane protein thiol group on erythrocyte membrane microviscoelasticities. Clin Hemorheol Microcirc, 1999; 21:137–146.
44.
CurraisA, MaherP. Functional consequences of age-dependent changes in glutathione status in the brain. Antioxid Redox Signal, 2013Online Ahead of PrintFebruary5, 2013, 23249101.
45.
KisicB, MiricD, ZoricL, IlicA, DragojevicI. Antioxidant capacity of lenses with age-related cataract. Oxid Med Cell Longev, 2012; 2012:467130.
46.
QadriSM, FöllerM, LangF. Inhibition of suicidal erythrocyte death by resveratrol. Life Sci, 2009; 85:33–38.
47.
LangF, GulbinsE, LercheH, HuberSM, KempeDS, FollerM. Eryptosis, a window to systemic disease. Cell Physiol Biochem, 2008; 22:373–380.
48.
ShaikN, AlhouraniE, BoscA, LiuG, TowhidS, LupescuA, LangF. Stimulation of suicidal erythrocyte death by ipratropium bromide. Cell Physiol Biochem, 2012; 30:1517–1525.
49.
BoocockDJ, FaustGE, PatelKR, SchinasAM, BrownVA, DucharmeMP, BoothTD, CrowellJA, PerloffM, GescherAJ, StewardWP, BrennerDE. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev, 2007; 16:1246–1252.
50.
WalleT, HsiehF, DeLeggeMH, OatisJEJr, WalleUK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos, 2004; 32:1377–1382.
El–MohsenMA, BayeleH, KuhnleG, GibsonG, DebnamE, SraiSKet al.Distribution of [3H]trans–resveratrol in rat tissues following oral administration. Br J Nutr, 2006; 96:62–70.
53.
Del PrincipeD, FregaG, SaviniI, CataniMV, RossiA, AviglianoL. The plasma membrane redox system in human platelet functions and platelet-leukocyte interactions. Thromb Haemost, 2009; 101:284–289.
54.
UngvariZ, Parrado-FernandezC, CsiszarA, de CaboR. Mechanisms underlying caloric restriction and lifespan regulation: Implications for vascular aging. Circ Res, 2008; 102:519–528.
55.
PhillipsJ P, CampbellSD, MichaudD, CharbonneauM, HillikerAJ. Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proc Natl Acad Sci USA, 1989; 86:2761–2765.
56.
MelovS, RavenscroftJ, MalikS, GillMS, WalkerDW, ClaytonPE, WallaceDC, MalfroyB, DoctrowSR, LithgowGJ. Extension of life-span with superoxide dismutase/catalase mimetics. Science, 2000; 289:1567–1569.
57.
MullerFL, SongW, LiuY, ChaudhuriA, Pieke-DahlS, StrongR, HuangTT, EpsteinC J, RobertsLJII, CseteM, FaulknerJA, Van RemmenH. Absence of CuZn superoxide dismutase leads to elevated oxidative stress andacceleration of age-dependent skeletal muscle atrophy. Free Radic Biol Med, 2006; 40:1993–2004.
