The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“DHA then ends up amounting to more than 50% of OS phospholipid fatty acyl chains and therefore DHA-containing phospholipids in the retina and other cells are reservoirs for docosanoids (Bazan et al., 1984; Mukherjee et al., 2004).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Mukherjee et al., 2004
In the citing paper
“In fact, NPD1 also induces the anti-apoptotic Bcl-2 family of proteins Bcl-2 and Bcl-xl in oxidatively challenged human RPE cells (Mukherjee et al., 2004) and promotes cytoprotection.”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Mukherjee et al., 2004
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Essential fatty acids in health and chronic disease
Simopoulos, A. P. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.3.560s · Cited by 1,703
Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., & Gronert, K. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.8.1197 · Cited by 1,189
Self-citationHong, S., Gronert, K., Devchand, P. R., Moussignac, R.-L., & Serhan, C. N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300218200 · Cited by 1,000
Self-citationMechanisms of action of docosahexaenoic acid in the nervous system
Salem, N., Litman, B., Kim, H., & Gawrisch, K. (2001) · Lipids · doi:10.1007/s11745-001-0805-6 · Cited by 919
Neuringer, M. D., CONNOR, W. E., Lin, D. S., Barstad, L., & Luck, S. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.11.4021 · Cited by 914
Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain
Bazán, N. G. (1970) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(70)90086-x · Cited by 855
Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305841200 · Cited by 802
Self-citationDietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys.
Neuringer, M., CONNOR, W. E., Petten, C. V., & Barstad, L. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111202 · Cited by 645
Birch, E. E., Garfield, S., Hoffman, D. R., Uauy, R. D., & Birch, D. G. (2000) · Developmental Medicine & Child Neurology · doi:10.1017/s0012162200000311 · Cited by 619
Effect of Dietary Omega-3 Fatty Acids on Retinal Function of Very-Low-Birth-Weight Neonates
Uauy, R. D., Birch, D. G., Birch, E. E., Tyson, J. E., & Hoffman, D. R. (1990) · Pediatric Research · doi:10.1203/00006450-199011000-00014 · Cited by 574
Flagged first, then by citations
Research works printed but not linked: 10
- Bazan, N. G. (1990) in Nutrition and the Brain, eds. Wurtman, R. J. & Wurtman, J. J. (Raven, New York), Vol. 8, pp. 1-24.
- Aveldaño di Caldironi, M. I. & Bazan, N. G. (1977) Adv. Exp. Med. Biol. 83, 249-256.411344
- Organisciak, D. T., Darrow, R. M., Jiang, Y. L. & Blanks, J. C. (1996) Invest. Ophthalmol. Vis. Sci. 37, 2243-2257.8843911
- Anderson, R. E, Maude, M. B. & Bok, D. (2001) Invest. Ophthalmol. Vis. Sci. 42, 1715-1720.11431433
- Bicknell, I. R., Darrow, R., Barsalou, L., Fliesler, S. J. & Organisciak, D. T. (2002) Mol. Vis. 8, 333-340.12355060
- Anderson, R. E, Maude, M. B., McClellan, M., Matthes, M. T., Yasumura, D. & LaVail, M. M. (2002) Mol. Vis. 8, 351-358.12355064
- Hu, J. & Bok, D. (2001) Mol. Vis. 7, 14-19.11182021
- Osborne, N. N., Cazevieillem C., Pergandem, G. & Wood, J. P. (1997) Invest. Ophthalmol. Vis. Sci. 38, 1390-1400.9191602
- Liang, Y. G., Jorgensen, A. G., Kaestel, C. G., Wiencke, A. K., Lui, G. M., la Cour, M. H., Ropke, C. H. & Nissen, M. H. (2000) Curr. Eye Res. 20, 25-34.10611712
- Sparrow, J. R. & Cai, B. (2001) Invest. Ophthalmol. Vis. Sci. 42, 1356-1362.11328751
Cited by
Sorted by citations
Items 701–750 of 750
The Effect of Docosahexaenoic Acid in a Mouse Model of Neuroinflammation
Orr, S. K. (2012) · TSpace (University of Toronto)
Aspartame-Induced Neurodegeneration Versus Omega 3 Alleviation
Ali, E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815238-6.00023-7
Antioxidative component of docosahexaenoic acid in the brain in diabetes
López-Malo, D., Arnal, E., Miranda, M., Johnsen‐Soriano, S., & Romero, F. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815776-3.00016-4
Falsini, B., Bush, R. A., & Sieving, P. A. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4557-0737-9.00037-0
Zhou, Y., Wang, J., Li, X., Li, K., Chen, L., Zhang, Z., & Peng, M. (2020) · doi:10.21203/rs.3.rs-28936/v1
Contribution of bioactive lipid mediators in neuroinflammation, resolution, and neuroprotection
Farooqui, A. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-88460-0.00011-4
Farooqui, A. A. (2009) · Springer eBooks · doi:10.1007/978-1-4419-0543-7_4
Andresen, M. C. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.13357410.14726835
Maternal DHA Impact on Child Neurodevelopment
Duttaroy, A. K. (2021) · MDPI eBooks · doi:10.3390/books978-3-0365-1615-8
Meleth, A. D., Raiji, V. R., Krishnadev, N., & Chew, E. Y. (2011) · Springer eBooks · doi:10.1007/978-3-642-20870-6_12
Catabolism of Plasmalogens in Brain
(2008) · Springer eBooks · doi:10.1007/978-0-387-77401-5_3
Roles of Phospholipases A2 in Brain
(2006) · Springer eBooks · doi:10.1007/978-0-387-49931-4_4
Resolvins and protectins: novel lipid mediators in anti-inflammation and resolution
Serhan, C. N. (2006) · Food & Nutrition Research · doi:10.3402/fnr.v50i0.1579
Leishmania mexicana Promotes Pain-reducing Metabolomic Reprogramming In Cutaneous LesionsPreprint
Volpedo, G., Oljuskin, T., Cox, B., Mercado, Y., Askwith, C. C., Azodi, N., Gannavaram, S., Nakhasi, H. L., & Satoskar, A. R. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.09.503319
Gorshunska, M. (2012) · PROBLEMS OF ENDOCRINE PATHOLOGY · doi:10.21856/j-pep.2012.4.19
Adult Diseases and Low-Grade Systemic Inflammation Have Their Origins in the Perinatal Period
Das, U. N. (2011) · Springer eBooks · doi:10.1007/978-94-007-0495-4_16
Aberrant lipid accumulation and retinal pigmental epithelium dysfunction in PRCD-deficient micePreprint
Motipally, S. I., Kolson, D. R., Guan, T., & Kolandaivelu, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.08.584131
New Insights into AMD Pathogenesis
Cheng, S.-Y., & Punzo, C. (2024) · Essentials in ophthalmology/Essentials ophthalmology · doi:10.1007/978-981-99-4436-1_12
Inflammation Resolution Mediators: Future Prospects
Müller, R. L. J., Hoch, M., & Gupta, S. K. (2024) · Springer eBooks · doi:10.1007/978-981-97-0157-5_9
Bakker, L. M., Boulton, M. E., & Rôżanowska, M. (2024) · Antioxidants · doi:10.3390/antiox13111428
“However, the protective effects of docosahexaenoate in experiments on cultured cells were demonstrated at concentrations several orders of magnitude smaller than its physiological concentrations in POS or those used in this study [13–17 , 90–”
InfluentialElovanoids: linking nutrition to neuroprotection
Bazan, N. G. (2026) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000001198
Marine-Derived Natural Bioactives for the Treatment of Stroke
Vijayarani, K. R., Keerthiga, M., Thenisaimozhi, A. T., Anbazhagan, S., Priya, R. R., Kassab, Y. W., & Ann, N. (2026) · Nutritional neurosciences · doi:10.1007/978-981-95-5791-2_12
Lee, J. Y., Lim, L. W. C., Wong, C.-Y., Koh, R. Y., Lim, C. L., Kok, Y.-Y., & Chye, S. M. (2026) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273403412251202093934
Bernard, J. Y. (2013) · theses.fr (ABES) · doi:10.70675/a3e0b8a6z4855z4a77za6ebz68e599d268ea
“Les docosanoïdes, tels que la neuroprotectine D1, dérivent du DHA et ont des effets anti-inflammatoires, anti-apoptotiques et neuroprotecteurs (Mukherjee et al., 2004).”
Jouvene, C. C. (2016) · theses.fr (ABES) · doi:10.70675/48490179zca84z4fb2z8a6dzbc32351d6d47
Caractérisation et prévention des conséquences d'un syndrome métabolique dans la rétine
Vidal, E. (2018) · theses.fr (ABES) · doi:10.70675/09e85feez27afz465az91aaz70fa8efb0c74
Touhami, S. (2018) · theses.fr (ABES) · doi:10.70675/906d91bcz2fb6z4a41zb6bez8e9eff5bb35b
Lipid metabolism and retinal diseases
Gabrielle, P. (2022) · theses.fr (ABES) · doi:10.70675/f4f26b37z43acz4da3zb19dz906bc95fe494
Ye, S.-Y., Qu, Y., Zhang, J.-H., Wang, X.-H., Wang, J., Xue, Y., & Liu, J.-D. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835168
“PD1 possesses powerful neuroprotective and anti-in fl ammatory effects, suppressing pro-in fl ammatory gene expression and promoting neuronal survival (142).”
Signaling lipids: An overview of emerging physiological functions
Saharan, O., Pal, T., & Kamat, S. S. (2026) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2026.102654
The Pro-resolving Mediators of Inflammation
Vlasakov, I., & Nshimiyimana, R. (2025) · Springer eBooks · doi:10.1007/978-3-031-55254-0_18-1
Moshtaghion, S. M., Shayan, M., Ramakrishnan, S., Ham, A., Gharehkoshan, A. S., Morley, M. G., Zebardast, N., Diaz-Corrales, F. J. J., Rodríguez-de-la-Rúa-Franch, E., Husain, D., et al. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1912337
“Enzymatic derivatives of DHA, most notably neuroprotectin D1 (NPD1), exert potent anti-inflammatory and anti-apoptotic actions in human RPE and neural retina (Mukherje et al., 2007; Mukherjee et al., 2004).”
Lipoxin A4 (LXA4) for diabetic retinopathy (DR)
Das, U. N. (2026) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_1985_25
“[9] Previously, we observed that plasma and vitreal content of Commentaries brain‑derived neurotrophic factors (BDNFs) and lipoxin A 4 are low, whereas IL‑6 and VEGF are increased in DR. [10] Altered Essential Fatty Acids (EFAs)”
Berrow, E. J. (2012) · Aston Publications Explorer (Aston University) · doi:10.48780/publications.aston.ac.uk.00016328
Is Diabetic Retinopathy (DR) a Lipoxin A4 (LXA4) and Arachidonic Acid (AA) Deficiency Disorder?
Das, U. N. (2026) · Recent trends in pharmacology. · doi:10.62425/rtpharma.1957627
Diet and environmental factors shape retinal lipid composition in common carp (Cyprinus carpio)
Pilecky, M., Sedlmayr, I., Kesti, P., Schnorr, S. L., Obermair, G. J., Kouba, A., & Kainz, M. J. (2026) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2026.102768
Serhan, C. N. (2026) · Current topics in microbiology and immunology · doi:10.1007/82_2026_354
Sun, K., Merilees, J., & Qiu, X. (2026) · Marine Drugs · doi:10.3390/md24100357
“DHA is highly enriched in the brain and retina, where it supports neuronal and visual function, while serving as a substrate for specialized pro-resolving mediators, including resolvins and neuropro-tectin D1 [3,4,20,21,85].”
Kotlyarov, S. (2026) · Studies in natural products chemistry · doi:10.1016/b978-0-443-51068-7.00014-3
Millar, B., Godson, C., & de Gaetano, M. (2026) · Current topics in microbiology and immunology · doi:10.1007/82_2026_367
Serhan, C. N., & Aliberti, J. (2014) · ASM Press eBooks · doi:10.1128/9781555816650.ch17
Membrane lipidomics: the reorganization of fatty acids as a biomarker of cell condition
Chatgilialoglu, A. (2009) · AMS Dottorato Institutional Doctoral Theses Repository (University of Bologna) · doi:10.6092/unibo/amsdottorato/2145
Metadata
- Authors
- Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N., & Bazan, N. G.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
