Online citations, reference lists, and bibliographies.
Referencing for people who value simplicity, privacy, and speed.
Get Citationsy
← Back to Search

Hydroxytyrosol Protects Against Oxidative Damage By Simultaneous Activation Of Mitochondrial Biogenesis And Phase II Detoxifying Enzyme Systems In Retinal Pigment Epithelial Cells.

L. Zhu, Zhongbo Liu, Z. Feng, J. Hao, W. Shen, Xuesen Li, Lijuan Sun, E. Sharman, Ying Wang, K. Wertz, P. Weber, X. Shi, J. Liu
Published 2010 · Medicine, Biology

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1α) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including γ-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1α led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress.
This paper references
10.1016/S0092-8674(00)80611-X
Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1
Z. Wu (1999)
10.1074/jbc.273.35.22528
Mice with a Homozygous Null Mutation for the Most Abundant Glutathione Peroxidase, Gpx1, Show Increased Susceptibility to the Oxidative Stress-inducing Agents Paraquat and Hydrogen Peroxide*
J. D. de Haan (1998)
10.3390/12081679
Phenolic molecules in virgin olive oils: a survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade.
A. Bendini (2007)
10.1111/j.1582-4934.2008.00390.x
Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease
H. Zhang (2010)
10.1113/jphysiol.2006.109512
The role of AMP‐activated protein kinase in mitochondrial biogenesis
Richard M. Reznick (2006)
10.1073/PNAS.91.23.10771
Oxidative damage and mitochondrial decay in aging.
M. Shigenaga (1994)
10.1016/S0076-6879(84)05015-1
Assays of glutathione peroxidase.
L. Flohe (1984)
10.1016/j.brainres.2006.10.004
The concept of “aldehyde load” in neurodegenerative mechanisms: Cytotoxicity of the polyamine degradation products hydrogen peroxide, acrolein, 3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a retinal ganglion cell line
P. Wood (2007)
10.1074/jbc.M704213200
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance*
C. Choi (2007)
10.1007/S11892-005-0006-3
Mitochondrial dysfunction and type 2 diabetes
R. Parish (2005)
10.1073/pnas.051618798
Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice
M. Ramos-Gómez (2001)
10.1007/s00125-006-0170-2
Mitochondria are impaired in the adipocytes of type 2 diabetic mice
HJ Choo (2006)
10.1016/S0003-2697(03)00143-X
Fluorescence-based microtiter plate assay for glutamate-cysteine ligase activity.
C. White (2003)
R-alpha-lipoic acid and acetyl-L-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes.
W. Shen (2008)
10.1021/JF000537W
Antioxidant activity of hydroxytyrosol acetate compared with that of other olive oil polyphenols.
M. Gordon (2001)
10.1073/PNAS.77.9.5216
Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity.
A. Benson (1980)
10.1002/MNFR.200700041
Nutrition in the genomics era: cardiovascular disease risk and the Mediterranean diet.
J. Ordovas (2007)
10.1017/S1368980007668530
Importance of functional foods in the Mediterranean diet.
R. Ortega (2006)
10.1126/SCIENCE.1079368
Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide
E. Nisoli (2003)
10.1073/pnas.172398899
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
A. Dinkova-Kostova (2002)
10.1016/J.TOX.2007.10.029
The Nrf2-Keap1 defence pathway: role in protection against drug-induced toxicity.
I. Copple (2008)
10.1167/IOVS.06-0248
Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid.
L. Jia (2007)
10.1371/journal.pone.0002328
A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats
W. Shen (2008)
10.1161/CIRCULATIONAHA.105.554360
Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity
S. Boudina (2005)
10.1016/j.freeradbiomed.2008.01.004
Lipoamide protects retinal pigment epithelial cells from oxidative stress and mitochondrial dysfunction.
Xuesen Li (2008)
10.1167/IOVS.04-1369
Flavonoids protect human retinal pigment epithelial cells from oxidative-stress-induced death.
A. Hanneken (2006)
10.1074/JBC.M407484200
Coenzyme Specificity of Sir2 Protein Deacetylases
M. T. Schmidt (2004)
10.1073/PNAS.0405432101
Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals.
E. Nisoli (2004)
10.1111/j.1582-4934.2008.00342.x
Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats
Jiejie Hao (2009)
10.1111/j.1749-6632.2002.tb02090.x
Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites
J. Liu (2002)
10.1111/j.1471-4159.2007.04954.x
Hydroxytyrosol protects retinal pigment epithelial cells from acrolein‐induced oxidative stress and mitochondrial dysfunction
Zhongbo Liu (2007)
10.1258/136218006779160481
Nutrition and cancer risk: an overview
E. Fernández (2006)
10.1016/J.OPHTHA.2003.11.010
Risk factors for incident age-related macular degeneration: pooled findings from 3 continents.
S. C. Tomany (2004)
10.1002/MNFR.200600308
Olive oil and oxidative stress.
M. Fitó (2007)
10.1016/j.cell.2006.09.024
Suppression of Reactive Oxygen Species and Neurodegeneration by the PGC-1 Transcriptional Coactivators
J. St-Pierre (2006)
10.1016/J.FREERADBIOMED.2005.09.032
Retinal degeneration from oxidative damage.
Celia Cingolani (2006)
10.1007/s11745-004-1351-y
Olive oil and modulation of cell signaling in disease prevention
K. Wahle (2004)
10.1016/j.bbabio.2009.01.003
UCP2, not a physiologically relevant uncoupler but a glucose sparing switch impacting ROS production and glucose sensing.
F. Bouillaud (2009)
10.1016/j.cell.2006.09.015
Transcriptional Repression of PGC-1α by Mutant Huntingtin Leads to Mitochondrial Dysfunction and Neurodegeneration
Libin Cui (2006)
10.1073/pnas.261572998
Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: The indirect antioxidant effects of sulforaphane
X. Gao (2001)
10.1016/J.MITO.2006.04.003
Acrolein is a mitochondrial toxin: effects on respiratory function and enzyme activities in isolated rat liver mitochondria.
Lijuan Sun (2006)
10.1016/0891-5849(91)90192-6
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.
H. Esterbauer (1991)
10.1002/jcp.20346
Oxidative damage is a potential cause of cone cell death in retinitis pigmentosa
J. Shen (2005)
10.1111/j.1755-3768.2008.01376.x
The epidemiology of age‐related macular degeneration in the Indian subcontinent
J. H. Woo (2009)
10.1073/PNAS.0400282101
Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid.
J. Suh (2004)
10.1126/SCIENCE.1071163
Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK
H. Wu (2002)
10.1016/S1532-0456(02)00180-1
Antioxidant effect of hydroxytyrosol (DPE) and Mn2+ in liver of cadmium-intoxicated rats.
E. Casalino (2002)
10.1249/01.MSS.0000106171.38299.64
AMP-activated protein kinase: a key system mediating metabolic responses to exercise.
D. Hardie (2004)
10.1089/ARS.2007.1787
Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment.
J. Balla (2007)
10.1007/s00125-007-0852-4
R-α-Lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes
W. Shen (2007)
10.1016/J.BBRC.2003.09.110
Induction of endogenous antioxidants and phase 2 enzymes by alpha-lipoic acid in rat cardiac H9C2 cells: protection against oxidative injury.
Z. Cao (2003)
10.1016/J.FREERADBIOMED.2007.03.034
Trends in oxidative aging theories.
F. Muller (2007)
10.1167/IOVS.02-0287
Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells.
N. Philp (2003)
10.14670/HH-22.1301
Oxidative damage in age-related macular degeneration.
J. Shen (2007)
10.1006/BBRC.2002.6614
Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells.
Z. Cao (2002)
10.1093/CARCIN/BGI068
Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes.
J. Fahey (2005)
10.1016/J.ATHEROSCLEROSIS.2007.04.006
Wine, research and cardiovascular disease: instructions for use.
A. Bertelli (2007)
10.1007/s11064-007-9403-0
The Effects and Mechanisms of Mitochondrial Nutrient α-Lipoic Acid on Improving Age-Associated Mitochondrial and Cognitive Dysfunction: An Overview
J. Liu (2007)
10.1073/PNAS.0505723102
Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducers.
T. Satoh (2006)



This paper is referenced by
10.1007/s11064-014-1315-1
Curcumin Prevents Cerebral Ischemia Reperfusion Injury Via Increase of Mitochondrial Biogenesis
L. Liu (2014)
10.1002/EJLT.201400423
Protectin DX, a double lipoxygenase product from DHA, inhibits the production of both inflammatory cytokines and reactive oxygen species in human retinal pigment epithelium cells
Yining Dai (2015)
10.5772/2374
Bioactive Compounds in Phytomedicine
I. Rasooli (2012)
10.1016/j.bcp.2014.04.001
Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.
S. Granados-Principal (2014)
10.1016/j.ejphar.2011.03.045
Hydroxytyrosol reduces intracellular reactive oxygen species levels in vascular endothelial cells by upregulating catalase expression through the AMPK-FOXO3a pathway.
H. Zrelli (2011)
10.1016/B978-0-12-802309-9.00022-4
Role of Natural Fermented Olives in Health and Disease
C. Peres (2016)
10.1007/s12640-014-9492-x
3,4-Dihydroxyphenylethanol Attenuates Spatio-Cognitive Deficits in an Alzheimer’s Disease Mouse Model: Modulation of the Molecular Signals in Neuronal Survival-Apoptotic Programs
M. ArunSundar (2014)
Hydroxytyrosol and oleuropein from olive leaves: Potent anti-inflammatory and analgesic activities
Ehsen Haloui (2011)
10.1016/J.AQUACULTURE.2017.02.013
Olive mill wastewater-enriched diet positively affects growth, oxidative and immune status and intestinal microbiota in the crayfish, Astacus leptodactylus
L. Parrillo (2017)
10.1016/j.numecd.2018.04.004
Olive oil and prevention of chronic diseases: Summary of an International conference.
F. Visioli (2018)
10.1002/9781118299753.CH10
Extra‐Virgin Olive Oil—Healthful Properties of its Phenolic Constituents
F. Visioli (2012)
10.1371/journal.pone.0160240
Olive Oil Consumption and Age-Related Macular Degeneration: The Alienor Study
A. Cougnard-Grégoire (2016)
10.3233/NUA-130016
Beneficial effects of olive oil phenols on the aging process: Experimental evidence and possible mechanisms of action
L. Giovannelli (2012)
10.1155/2013/590379
Assessing Competence of Broccoli Consumption on Inflammatory and Antioxidant Pathways in Restraint-Induced Models: Estimation in Rat Hippocampus and Prefrontal Cortex
L. Khalaj (2013)
10.1007/978-3-642-22144-6_156
Biological Activity of Oleuropein and its Derivatives
S. Bulotta (2013)
10.1016/j.jnutbio.2017.09.009
Involvement of bilitranslocase and beta-glucuronidase in the vascular protection by hydroxytyrosol and its glucuronide metabolites in oxidative stress conditions.
Julien Peyrol (2018)
10.1017/S1751731119001356
(-)-Epigallocatechin-3-gallate and hydroxytyrosol improved antioxidative and anti-inflammatory responses in bovine mammary epithelial cells.
L. Basiricò (2019)
10.3390/antiox9090885
Retinoprotective Effect of Wild Olive (Acebuche) Oil-Enriched Diet against Ocular Oxidative Stress Induced by Arterial Hypertension
Álvaro Santana-Garrido (2020)
10.1002/mnfr.201300747
Targeting mitochondrial alterations to prevent type 2 diabetes--evidence from studies of dietary redox-active compounds.
Z. Cheng (2014)
10.1111/1440-1681.12211
Aerobic interval training protects against myocardial infarction‐induced oxidative injury by enhancing antioxidase system and mitochondrial biosynthesis
Hong-Ke Jiang (2014)
10.3390/ijms21093050
Exposure of Triclosan in Porcine Oocyte Leads to Superoxide Production and Mitochondrial-Mediated Apoptosis during In Vitro Maturation
H. Park (2020)
10.1007/978-3-319-17121-0_53
The Potential Use of PGC-1α and PGC-1β to Protect the Retina by Stimulating Mitochondrial Repair.
Carolina Abrahan (2016)
10.1002/9781119135340.CH22
Olives and Olive Oil: A Mediterranean Source of Polyphenols
A. Tresserra-Rimbau (2017)
10.3390/ijms19092757
Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis
Tanila Wood Dos Santos (2018)
10.1080/1028415X.2018.1469281
The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat
C. Conde (2018)
10.1016/j.drudis.2013.11.002
NF-κβ signaling and chronic inflammatory diseases: exploring the potential of natural products to drive new therapeutic opportunities.
Matthew J. Killeen (2014)
10.1016/j.mito.2020.03.002
Combination therapy with astaxanthin and epidermal neural crest stem cells improves motor impairments and activates mitochondrial biogenesis in a rat model of spinal cord injury.
L. Mohaghegh Shalmani (2020)
Procédés et compositions pour inhiber le stress oxydatif
Constance L. Cepko (2014)
10.3109/01480545.2013.878950
Antioxidant role of hydroxytyrosol on oxidative stress in cadmium-intoxicated rats: different effect in spleen and testes
Elisabetta Merra (2014)
10.1016/j.phrs.2019.01.045
Secoiridoids of olive and derivatives as potential coadjuvant drugs in cancer: A critical analysis of experimental studies
M. Celano (2019)
Extra virgin olive oil reduces liver oxidative stress and tissue depletion of long-chain polyunsaturated fatty acids produced by a high saturated fat diet in mice
R. Valenzuelaa (2016)
10.3390/antiox9080685
Structure–Biological Activity Relationships of Extra-Virgin Olive Oil Phenolic Compounds: Health Properties and Bioavailability
Paloma Rodríguez-López (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar