Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.

Abstract

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.

• Authors: Lu Zhu, Zhongbo Liu, Zhihui Feng, Jiejie Hao, Weili Shen, Xuesen Li, Lijuan Sun, Edward Sharman, Ying Wang, Karin Wertz, Peter Weber, Xianglin Shi, Jiankang Liu
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 21 Issue 11 Pg. 1089-98 (Nov 2010) ISSN: 1873-4847 [Electronic] United States
• PMID: 20149621 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• DNA-Binding Proteins
• Flavonoids
• Ion Channels
• Mitochondrial Proteins
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• PPAR alpha
• Phenols
• Polyphenols
• Transcription Factors
• UCP2 protein, human
• Uncoupling Protein 2
• mitochondrial transcription factor A
• 3,4-dihydroxyphenylethanol
• Acrolein
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• Phenylethyl Alcohol

Topics

• Acrolein (adverse effects, metabolism)
• Antioxidants (pharmacokinetics)
• Cell Line
• DNA-Binding Proteins (metabolism)
• Dietary Supplements
• Flavonoids (metabolism)
• Humans
• Ion Channels (metabolism)
• Macular Degeneration (metabolism)
• Metabolic Detoxication, Phase II
• Mitochondria (metabolism)
• Mitochondrial Proteins (metabolism)
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress
• PPAR alpha (metabolism)
• Phenols (metabolism)
• Phenylethyl Alcohol (analogs & derivatives, pharmacokinetics)
• Pigment Epithelium of Eye (cytology, drug effects, metabolism)
• Polyphenols
• Transcription Factors (metabolism)
• Uncoupling Protein 2