Cited by 753Fatty Acid Research and HealthRetinal Diseases and TreatmentsAntioxidant Activity and Oxidative Stress

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Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

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Mukherjee, Pranab K., Marcheselli, Victor L., Serhan, Charles N., Bazan, Nicolas G.·2004·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0402531101PMC PMC420421

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Abstract

Docosahexaenoic acid (DHA) is a lipid peroxidation target in oxidative injury to retinal pigment epithelium (RPE) and retina. Photoreceptor and synaptic membranes share the highest content of DHA of all cell membranes. This fatty acid is required for RPE functional integrity; however, it is not known whether specific mediators generated from DHA contribute to its biological significance. We used human ARPE-19 cells and demonstrated the synthesis of 10,17S-docosatriene [neuroprotectin D1 (NPD1)]. This synthesis was enhanced by the calcium ionophore A-23187, by IL-1beta, or by supplying DHA. Under these conditions, there is a time-dependent release of endogenous free DHA followed by NPD1 formation, suggesting that phospholipase A(2) releases the mediator's precursor. Added NPD1 potently counteracted H(2)O(2)/tumor necrosis factor alpha oxidative-stress-triggered apoptotic RPE DNA damage. NPD1 also up-regulated the antiapoptotic proteins Bcl-2 and Bcl-x(L) and decreased proapoptotic Bax and Bad expression. Moreover, NPD1 (50 nM) inhibited oxidative-stress-induced caspase-3 activation. NPD1 also inhibited IL-1beta-stimulated expression of cyclooxygenase 2 promoter transfected into ARPE-19 cells. Overall, NPD1 protected RPE cells from oxidative-stress-induced apoptosis, and we predict that it will similarly protect neurons. This lipid mediator therefore may indirectly contribute to photoreceptor cell survival as well. Because both RPE and photoreceptor cells die in retinal degenerations, our findings contribute to the understanding of retinal cell survival signaling and potentially to the development of new therapeutic strategies.

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Authors: Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N., & Bazan, N. G.
Affiliations: Louisiana State University (US)
Corresponding author: Bazan, Nicolas G.
ORCID: Mukherjee, Pranab K.
Serhan, Charles N.
Bazan, Nicolas G.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2004-05-19
Volume: 101
Issue: 22
Pages: 8491-8496
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0402531101
PMC: PMC420421
OpenAlex: W1739691545
Cited by: 753
References: 50
Citations by year: 2026: 22 · 2025: 14 · 2024: 13 · 2023: 14 · 2022: 24 · 2021: 20 · 2020: 34 · 2019: 23 · 2018: 25 · 2017: 34 · 2016: 24 · 2015: 35 · 2014: 42 · 2013: 52 · 2012: 42
FWCI: 44.10
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Huntsman Cancer Institute
University of Leicester
National Institutes of Health (4r37gm038765-19, GM 38765)
National Eye Institute (EY05121, R01EY005121)
National Institute of General Medical Sciences (GM 38765, R01GM038765, R37-GM038765)
National Center for Research Resources (P20RR-16816, 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, docosahexaenoic acid, retinal pigment epithelium, oxidative stress, apoptosis, phospholipase A2, cyclooxygenase-2, Bcl-2 family proteins, caspase-3, IL-1β, photoreceptor survival, retinal degeneration, lipid mediators
MeSH terms: Cell Line, Docosahexaenoic Acids, Epithelial Cells, Humans, Interleukin-1, Isoenzymes, Membrane Proteins, Pigment Epithelium of Eye, Prostaglandin-Endoperoxide Synthases, Lipid Peroxidation, Molecular Structure, Apoptosis, Oxidative Stress, Proto-Oncogene Proteins c-bcl-2, Caspases, Cyclooxygenase 2, Caspase 3, DNA Fragmentation

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Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress

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