Cited by 104Fatty Acid Research and HealthRetinal Diseases and TreatmentsAntioxidant Activity and Oxidative Stress

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Selective Survival Rescue in 15-Lipoxygenase-1-deficient Retinal Pigment Epithelial Cells by the Novel Docosahexaenoic Acid-derived Mediator, Neuroprotectin D1

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Calandria, Jorgelina M., Marcheselli, Victor L., Mukherjee, Pranab K., Uddin, Jasim, Winkler, Jeremy W., Petasis, Nicos A., Bazan, Nicolas G.·2009·Journal of Biological Chemistry

DOI 10.1074/jbc.m109.003988PMC PMC2719426

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Abstract

The integrity of the retinal pigment epithelial (RPE) cell is essential for the survival of rod and cone photoreceptor cells. Several stressors, including reactive oxygen species, trigger apoptotic damage in RPE cells preceded by an anti-inflammatory, pro-survival response, the formation of neuroprotectin D1 (NPD1), an oxygenation product derived from the essential omega-3 fatty acid family member docosahexaenoic acid. To define the ability of NPD1 and other endogenous novel lipid mediators in cell survival, we generated a stable knockdown human RPE (ARPE-19) cell line using short hairpin RNA to target 15-lipoxygenase-1. The 15-lipoxygenase-1-deficient cells exhibited 30% of the protein expression, and 15-lipoxygenase-2 remained unchanged, as compared with an ARPE-19 cell line control established using nonspecific short hairpin RNA transfected cells. NPD1 synthesis was stimulated by tumor necrosis factor alpha/H2O2-mediated oxidative stress in nonspecific cells (controls), whereas in silenced cells, negligible amounts of NPD1, 12(S)- and 15(S)-hydroxyeicosatetraenoic acid, and lipoxin A4 were found under these conditions. Neither control nor the deficient cells showed an increase in 15-lipoxygenase-1 protein content after 16 h of oxidative stress, suggesting that the increased activity of 15-lipoxygenase-1 is due to activation of pre-existing proteins. 15-Lipoxygenase-silenced cells also displayed an exacerbated sensitivity to oxidative stress-induced apoptosis when compared with the control cells. NPD1 selectively and potently rescued 15-lipoxygenase-silenced cells from oxidative stress-induced apoptosis. These results demonstrate that 15-lipoxygenase-1 is activated by oxidative stress in ARPE-19 cells and that NPD1 is part of an early survival signaling in RPE cells.

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Authors: Calandria, J. M., Marcheselli, V. L., Mukherjee, P. K., Uddin, J., Winkler, J. W., Petasis, N. A., & Bazan, N. G.
Affiliations: Louisiana State University (US)
University of Southern California (US)
Corresponding author: Bazan, Nicolas G.
ORCID: Calandria, Jorgelina M.
Mukherjee, Pranab K.
Uddin, Jasim
Petasis, Nicos A.
Bazan, Nicolas G.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2009-06
Volume: 284
Issue: 26
Pages: 17877-17882
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m109.003988
PMC: PMC2719426
OpenAlex: W2022004671
Cited by: 104
References: 33
Citations by year: 2026: 1 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 9 · 2016: 5 · 2015: 9 · 2014: 2 · 2013: 10 · 2012: 9
FWCI: 10.97
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 4151 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (EY0-05121, RR016816)
National Eye Institute (R01EY005121)
National Center for Research Resources (P20RR016816)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: neuroprotectin D1, 15-lipoxygenase-1, retinal pigment epithelial cells, docosahexaenoic acid, oxidative stress, apoptosis, lipoxin A4, hydroxyeicosatetraenoic acids, photoreceptor survival, ARPE-19 cells
MeSH terms: Arachidonate 15-Lipoxygenase, Docosahexaenoic Acids, Humans, Hydrogen Peroxide, Immunoenzyme Techniques, Pigment Epithelium of Eye, Retina, Tumor Necrosis Factor-alpha, Blotting, Western, Lipoxygenase Inhibitors, Oxidants, Apoptosis, Oxidative Stress, RNA, Small Interfering, Lipoxins

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Selective Survival Rescue in 15-Lipoxygenase-1-deficient Retinal Pigment Epithelial Cells by the Novel Docosahexaenoic Acid-derived Mediator, Neuroprotectin D1

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