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Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells.
Mol Vis. 2014; 20:760-9.MV

Abstract

PURPOSE

In this work, we investigated the ability of pinosylvin (PS), 3,5-dihydroxy-trans-stilbene, to modulate oxidative stress in human RPE cells. PS, a stilbenoid polyphenol, occurs in high concentrations in bark byproducts and therefore represents an attractive bioactive compound for health-promoting applications.

METHODS

First, we evaluated the toxicity range of PS by exposing ARPE-19 cells to 0.1-200 µM concentrations of PS for 24 h followed by the cell viability test. In the next stage, the ARPE-19 cells were preincubated in PS for 24 h followed by hydroquinone (HQ) exposure without PS for another 24 h. The cell viability test was conducted after HQ exposure. To elucidate the potential mechanisms behind PS-mediated protection against oxidative stress, the ARPE-19 cells were treated with 5 µM PS for 6 h, and mRNA was extracted at four time points (2 h, 6 h, 12 h, 24 h) to determine changes in the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), sequestosome 1 (p62/SQSTM1), heme oxygenase-1 (HO-1), and glutathione S-transferase pi 1 (GSTP1) genes. To clarify the molecular mechanism behind PS-mediated protection further, the ARPE-19 cells were transfected with p62 and Nrf2 siRNAs for 24 h, and the roles of p62, Nrf2, and its target gene HO-1 in conferring protection against oxidative stress were studied with quantitative real-time PCR (qRT-PCR) and the cell viability test.

RESULTS

PS treatment at concentrations of 5 and 10 µM significantly enhanced cell survival from oxidative stress. The expression levels of an enzyme with antioxidative, anti-inflammatory, and immunomodulatory properties, HO-1, were increased by PS treatment and correlated strongly with cell survival. PS treatment did not elevate the expression levels of Nrf2 or its target genes, p62 or GSTP1, even though it had a clear effect on the expression of HO-1, another gene controlled by Nrf2. RNA interference analysis further confirmed the important role of Nrf2 and HO-1 in PS-mediated protection against oxidative stress whereas the role of p62 seemed to be insignificant at the gene expression and cell viability levels.

CONCLUSIONS

Our results suggest that PS treatment conferred protection against oxidative stress through the induction of HO-1 in human RPE cells. Consequently, PS-stilbene compounds, which can be isolated in significant amounts from bark waste, may possess health-promoting properties against aging-related diseases associated with oxidative stress such as age-related macular degeneration (AMD) and Alzheimer's disease. These natural compounds may offer opportunities for high-value use of bark waste in diverse health-related applications.

Authors+Show Affiliations

Department of Biology, University of Eastern Finland, Kuopio, Finland ; Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.Department of Biology, University of Eastern Finland, Kuopio, Finland ; Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland ; Department of Ophthalmology, University Hospital Kuopio, Kuopio, Finland.Department of Biology, University of Eastern Finland, Kuopio, Finland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24940030

Citation

Koskela, Ali, et al. "Pinosylvin-mediated Protection Against Oxidative Stress in Human Retinal Pigment Epithelial Cells." Molecular Vision, vol. 20, 2014, pp. 760-9.
Koskela A, Reinisalo M, Hyttinen JM, et al. Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells. Mol Vis. 2014;20:760-9.
Koskela, A., Reinisalo, M., Hyttinen, J. M., Kaarniranta, K., & Karjalainen, R. O. (2014). Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells. Molecular Vision, 20, 760-9.
Koskela A, et al. Pinosylvin-mediated Protection Against Oxidative Stress in Human Retinal Pigment Epithelial Cells. Mol Vis. 2014;20:760-9. PubMed PMID: 24940030.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pinosylvin-mediated protection against oxidative stress in human retinal pigment epithelial cells. AU - Koskela,Ali, AU - Reinisalo,Mika, AU - Hyttinen,Juha M T, AU - Kaarniranta,Kai, AU - Karjalainen,Reijo O, Y1 - 2014/06/02/ PY - 2013/11/23/received PY - 2014/05/30/accepted PY - 2014/6/19/entrez PY - 2014/6/19/pubmed PY - 2014/10/1/medline SP - 760 EP - 9 JF - Molecular vision JO - Mol. Vis. VL - 20 N2 - PURPOSE: In this work, we investigated the ability of pinosylvin (PS), 3,5-dihydroxy-trans-stilbene, to modulate oxidative stress in human RPE cells. PS, a stilbenoid polyphenol, occurs in high concentrations in bark byproducts and therefore represents an attractive bioactive compound for health-promoting applications. METHODS: First, we evaluated the toxicity range of PS by exposing ARPE-19 cells to 0.1-200 µM concentrations of PS for 24 h followed by the cell viability test. In the next stage, the ARPE-19 cells were preincubated in PS for 24 h followed by hydroquinone (HQ) exposure without PS for another 24 h. The cell viability test was conducted after HQ exposure. To elucidate the potential mechanisms behind PS-mediated protection against oxidative stress, the ARPE-19 cells were treated with 5 µM PS for 6 h, and mRNA was extracted at four time points (2 h, 6 h, 12 h, 24 h) to determine changes in the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), sequestosome 1 (p62/SQSTM1), heme oxygenase-1 (HO-1), and glutathione S-transferase pi 1 (GSTP1) genes. To clarify the molecular mechanism behind PS-mediated protection further, the ARPE-19 cells were transfected with p62 and Nrf2 siRNAs for 24 h, and the roles of p62, Nrf2, and its target gene HO-1 in conferring protection against oxidative stress were studied with quantitative real-time PCR (qRT-PCR) and the cell viability test. RESULTS: PS treatment at concentrations of 5 and 10 µM significantly enhanced cell survival from oxidative stress. The expression levels of an enzyme with antioxidative, anti-inflammatory, and immunomodulatory properties, HO-1, were increased by PS treatment and correlated strongly with cell survival. PS treatment did not elevate the expression levels of Nrf2 or its target genes, p62 or GSTP1, even though it had a clear effect on the expression of HO-1, another gene controlled by Nrf2. RNA interference analysis further confirmed the important role of Nrf2 and HO-1 in PS-mediated protection against oxidative stress whereas the role of p62 seemed to be insignificant at the gene expression and cell viability levels. CONCLUSIONS: Our results suggest that PS treatment conferred protection against oxidative stress through the induction of HO-1 in human RPE cells. Consequently, PS-stilbene compounds, which can be isolated in significant amounts from bark waste, may possess health-promoting properties against aging-related diseases associated with oxidative stress such as age-related macular degeneration (AMD) and Alzheimer's disease. These natural compounds may offer opportunities for high-value use of bark waste in diverse health-related applications. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/24940030/Pinosylvin_mediated_protection_against_oxidative_stress_in_human_retinal_pigment_epithelial_cells_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24940030/ DB - PRIME DP - Unbound Medicine ER -