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

Mukherjee, Pranab K.; Marcheselli, Victor L.; Serhan, Charles N.; Bazan, Nicolas G.

doi:10.1073/pnas.0402531101

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

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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DHA amounts to more than 50% of outer segment phospholipid fatty acyl chains, and DHA-containing phospholipids in the retina and other cells are reservoirs for docosanoids.
“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
NPD1 also induces the anti-apoptotic Bcl-2 family of proteins Bcl-2 and Bcl-xl in oxidatively challenged human RPE cells and promotes cytoprotection.
“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

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Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932 · see citing works
“and neural systems that has been documented in studies by Bazan and colleague”
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n−3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases
Calder, P. C. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.6.1505s · Cited by 2,525 · see citing works
Eicosanoid storm in infection and inflammation
Dennis, E. A., & Norris, P. C. (2015) · Nature Reviews Immunology · doi:10.1038/nri3859 · Cited by 1,517 · see citing works
Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators
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“DHA and NPD1 are neuroprotective in the retina (128), CNS, and brain (68), and PD1/NPD1 and resolvins may protect in early-stage Alzheimer’s as well as in ischemic stroke (124, 129).”
The Opposing Effects of N-3 and n-6 Fatty Acids
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Emerging targets in neuroinflammation-driven chronic pain
Ji, R., Xu, Z., & Gao, Y. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4334 · Cited by 1,102 · see citing works
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Serhan, C. N., Yang, R., Martinod, K., Kasuga, K., Pillai, P. S., Porter, T. F., Oh, S. F., & Spite, M. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081880 · Cited by 908 · see citing works
A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease
Lukiw, W. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25420 · Cited by 873 · see citing works
“The unesterified DHA pool size assessed by liquid chromatography–photodiode array–electrospray ionization–tandem mass spectrometry–based (LC-PDA-ESI-MS-MS–based) lipidomic analysis (5, 6) (Figure 1I) showed that neither Aβ42 nor sAPPα was able to promote unesterFigure 2 Aβ42-induced apoptosis is inhibited by NPD1 in H…”
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“LOX oxylipins 14,20-DiHDoHE Inhibits PMN infiltration in the mouse peritonitis model (101) 14,21-DiHDoHE Enhances wound healing in murine models (313, 314) 4-HDoHE Inhibits endothelial cell proliferation and sprouting angiogenesis in mouse model of oxygen-induced retinopathy (315) 7-HDoHE Activates PPARg in transfecte…”
Polyunsaturated fatty acids and inflammatory processes: New twists in an old tale
Calder, P. C. (2009) · Biochimie · doi:10.1016/j.biochi.2009.01.008 · Cited by 721 · see citing works
“Metabolism of DHA initially by 15-lipoxygenase and then a series of other reactions generates a dihydroxy derivative termed neuroprotectin D1 (also called protectin D1), again a potent antiinflammatory molecule in neutrophils, macrophages, T cells, and microglia [25,28].”
A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model
Lim, G. P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O. J., Salem, N., Frautschy, S. A., & Cole, G. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4225-04.2005 · Cited by 687 · see citing works
Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
Connor, K. M., SanGiovanni, J. P., Löfqvist, C., Aderman, C. M., Chen, J., Higuchi, A., Hong, S., Pravda, E. A., Majchrzak, S. F., Carper, D. A., et al. (2007) · Nature Medicine · doi:10.1038/nm1591 · Cited by 687 · see citing works
“Furthermore, the metabolites NPD1, RvD1 and RvE1 dose-dependently reduce Tnf mRNA expression in macrophages in culture and in other inflammatory model”
Polyunsaturated fatty acids and fatty acid-derived lipid mediators: Recent advances in the understanding of their biosynthesis, structures, and functions
Dyall, S. C., Balas, L., Bazan, N. G., Brenna, J. T., Chiang, N., Souza, F. D. C., Dalli, J., Durand, T., Galano, J., Lein, P. J., et al. (2022) · Progress in Lipid Research · doi:10.1016/j.plipres.2022.101165 · Cited by 679 · see citing works
“Hence, while produced and functions in neural systems, the prefix (neuro)protectin D1 was introduced [130], and in the immune system, it is PD1 [134].”
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Essential Fatty Acids: Biochemistry, Physiology and Pathology
Das, U. N. (2006) · Biotechnology Journal · doi:10.1002/biot.200600012 · Cited by 650 · see citing works
“These studies suggest that people who are genetically or otherwise predisposed to the disease may be able to delay it by increasing their DHA intake [79, 94].”
Polyunsaturated fatty acids and inflammation
Calder, P. C. (2006) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2006.05.012 · Cited by 640 · see citing works
“In addition, DHAderived mediators termed D-series resolvins, docosatrienes and neuroprotectins, also produced by COX-2/ LOX under some conditions, have been identified and these too appear to be anti-inflammatory and inflammation resolving [22–24].”
The Retinal Pigment Epithelium in Health and Disease
Sparrrow, J. R., Hicks, D., & Hamel, C. (2010) · Current Molecular Medicine · doi:10.2174/156652410793937813 · Cited by 625 · see citing works
Lipid Mediators in Health and Disease: Enzymes and Receptors as Therapeutic Targets for the Regulation of Immunity and Inflammation
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Treating inflammation and infection in the 21st century: new hints from decoding resolution mediators and mechanisms
Serhan, C. N. (2017) · The FASEB Journal · doi:10.1096/fj.201601222r · Cited by 553 · see citing works
“1) with the ABBREVIATIONS: DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HDHA, hydroxy-docosahexaenoic acid; LC-MS-MS, liquid chromatography– tandem mass spectrometry; LOX, lipoxygenase; LT, leukotriene; LX, lipoxin; MaR, maresin; MCTR, maresin conjugate in tissue regeneration; NPD1, neuroprotectin D1; NSAID,…”
Retinal light damage: Mechanisms and protection
Organisciak, D. T., & Merriman, D. K. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.11.004 · Cited by 546 · see citing works
Oxidative stress in the brain: Novel cellular targets that govern survival during neurodegenerative disease
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Saravanan, P., Davidson, N. C., Schmidt, E. B., & Calder, P. C. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60445-x · Cited by 510 · see citing works
Anti-Inflammatory and Proresolving Lipid Mediators
Serhan, C. N., Yacoubian, S., & Yang, R. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.151409 · Cited by 511 · see citing works
Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome
Serhan, C. N., Dalli, J., Colas, R. A., Winkler, J. W., & Chiang, N. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.006 · Cited by 492 · see citing works
“Given its potent protective actions in the retina and brain, we initially termed this bioactive mediator neuroprotectin D1 (NPD1) [12,14,72].”
Influential
Action of epoxyeicosatrienoic acids on cellular function
Spector, A. A., & Norris, A. W. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00402.2006 · Cited by 480 · see citing works
“Another epoxide derivative of DHA, 16,17-epoxy-docosatriene, is an intermediate in the pathway that produces neuroprotectin D1 in human ARPE-19 cells (113).”
Modulation of inflammation in brain: A matter of fat
Farooqui, A. A., Horrocks, L. A., & Farooqui, T. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04371.x · Cited by 460 · see citing works
Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival
Akbar, M. D., Calderón, F. H., Wen, Z., & Kim, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502903102 · Cited by 466 · see citing works
The Retinal Pigment Epithelium: Something More than a Constituent of the Blood-Retinal Barrier—Implications for the Pathogenesis of Diabetic Retinopathy
Simó, R., Villarroel, M., Corraliza, L., Hernández, C., & García‐Ramírez, M. (2010) · BioMed Research International · doi:10.1155/2010/190724 · Cited by 461 · see citing works
“Apart from the RPE’s functional integrity, DHA is the precursor of neuroprotectin D1 (NPD1), a docosatriene that protects RPE cells from oxidative stress [15, 16].”
Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: Their role and involvement in neurological disorders
Phillis, J. W., Horrocks, L. A., & Farooqui, A. A. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.02.002 · Cited by 456 · see citing works
Anti-Inflammatory Actions of Neuroprotectin D1/Protectin D1 and Its Natural Stereoisomers: Assignments of Dihydroxy-Containing Docosatrienes
Serhan, C. N., Gotlinger, K. H., Hong, S., Lu, Y., Siegelman, J. N., Baer, T. E., Yang, R., Colgan, S. P., & Petasis, N. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.3.1848 · Cited by 457 · see citing works
“, 10,17-dihydroxydocosatriene (1, 3, 37); its potent role in neural protection was recently uncovered (2), and thus it is denoted as NPD1 when produced in neural tissues.”
Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases
Calder, P. C. (2008) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200700289 · Cited by 457 · see citing works
Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases
Bazan, N. G., Molina, M. F., & Gordon, W. C. (2011) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104635 · Cited by 441 · see citing works
Endogenous pro‐resolving and anti‐inflammatory lipid mediators: a new pharmacologic genus
Serhan, C. N., & Chiang, N. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707489 · Cited by 428 · see citing works
“NPD1 limits stroke brain injury in part by reducing the entry of activated PMN to the stroke area (Marcheselli et al., 2003) and retinal pigmented cellular damage and promotes brain cell survival, suppressing Ab42-induced neurotoxicity (Mukherjee et al., 2004) (Table 5).”
Influential
Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation
Serhan, C. N. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100322 · Cited by 421 · see citing works
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Nutrition in Brain Development and Aging: Role of Essential Fatty Acids
Uauy, R. D., & Dangour, A. D. (2006) · Nutrition Reviews · doi:10.1301/nr.2006.may.s24-s33 · Cited by 417 · see citing works
Natural resolution of inflammation
Freire, M., & Dyke, T. E. V. (2013) · Periodontology 2000 · doi:10.1111/prd.12034 · Cited by 391 · see citing works
A neuroscientist's guide to lipidomics
Piomelli, D., Astarita, G., & Rapaka, R. S. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2233 · Cited by 380 · see citing works
Resolvins and protectins in the termination program of acute inflammation
Ariel, A., & Serhan, C. N. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.02.007 · Cited by 379 · see citing works
Inhibitors of Brain Phospholipase A2 Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders
Farooqui, A. A., Ong, W., & Horrocks, L. A. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.7 · Cited by 368 · see citing works
“The generation of docosanoids may 604 FAROOQUI ET AL. be an internal protective mechanism for preventing brain damage (Horrocks and Farooqui, 2004; Mukherjee et al., 2004; Serhan et al., 2004).”
Neuroprotectin D1 (NPD1): A DHA-Derived Mediator that Protects Brain and Retina Against Cell Injury-Induced Oxidative Stress
Bazan, N. G. (2006) · Brain Pathology · doi:10.1111/j.1750-3639.2005.tb00513.x · Cited by 367 · see citing works
“The newly isolated dihydroxy-containing DHA derivative from RPE and brain cells is called “neuroprotectin D1” (NPD1): i) because of its neuroprotective properties in brain ischemia-reperfusion (34) and in oxidative stress-challenged RPE cells (40), ii) because of its potent ability to inactivate pro-apoptotic signalin…”
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Novel Lipid Mediators Promote Resolution of Acute Inflammation
Spite, M. R., & Serhan, C. N. (2010) · Circulation Research · doi:10.1161/circresaha.110.223883 · Cited by 368 · see citing works
Protectin D1 Is Generated in Asthma and Dampens Airway Inflammation and Hyperresponsiveness
Levy, B. D., Kohli, P., Gotlinger, K. H., Haworth, O., Hong, S., Kazani, S. D., Israel, E., Haley, K. J., & Serhan, C. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.1.496 · Cited by 357 · see citing works
“In the nervous system, PD1 decreases brain leukocyte infiltration, IL-1 -induced NF- B activation, and cyclooxygenase-2 expression to elicit neuroprotection (12, 17).”
Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors
Bazan, N. G. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.03.005 · Cited by 353 · see citing works
Resolvins, docosatrienes, and neuroprotectins, novel omega‐3‐derived mediators, and their endogenous aspirin‐triggered epimers
Serhan, C. N., Arita, M., Hong, S., & Gotlinger, K. H. (2004) · Lipids · doi:10.1007/s11745-004-1339-7 · Cited by 349 · see citing works
“Neuroprotectin D1 Human whole blood, human PMN murine brain stroke (14) (10,17S-docosatriene) and its omega carbon-22 oxidation product, AT-RvD2 Murine inflammatory exudates (12) human glial cells (13); murine brain stroke (14); AT-RvD3 Murine inflammatory exudates (12) human retinal pigment epithelium ( 15 ) AT-RvD4…”
Influential
Are all n-3 polyunsaturated fatty acids created equal?
Anderson, B. M., & David, W. L. (2009) · Lipids in Health and Disease · doi:10.1186/1476-511x-8-33 · Cited by 335 · see citing works
Resolvin D Series and Protectin D1 Mitigate Acute Kidney Injury
Duffield, J. S., Hong, S., Vaidya, V. S., Lu, Y., Fredman, G., Serhan, C. N., & Bonventre, J. V. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.9.5902 · Cited by 335 · see citing works
“PD1, also known as NPD1 when generated in neuronal tissues (41, 49), is protective in the brain (33).”
Old and new generation lipid mediators in acute inflammation and resolution
Stables, M. J., & Gilroy, D. W. (2010) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.07.005 · Cited by 333 · see citing works
Polyunsaturated fatty acids and inflammation
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Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors
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“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript MaR1 maresin 1 (7R, 14S-dihydroxy-docosa-4Z, 8E, 10E, 12Z, 16Z, 19Z-hexaenoic acid) PD protectin PD1 protectin D1 (10R, 17S-dihydroxy-docosa-4Z, 7Z, 11E, 13E, 15Z, 19Z-hexaenoic acid), also known as neuroprotectin D1 (NPD1) Rv resolving Rv…”
Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their aspirin-triggered endogenous epimers: an overview of their protective roles in catabasis
Serhan, C. N., Gotlinger, K. H., Hong, S., & Arita, M. (2004) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2004.03.005 · Cited by 311 · see citing works
Neurological Benefits of Omega-3 Fatty Acids
Dyall, S. C., & Michael-Titus, A. T. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8036-z · Cited by 307 · see citing works
“It has been shown that under certain conditions DHA can be metabolised to oxygenated compounds with anti-inflammatory properties, such as 10-17S-docosatriene (also called neuroprotectin D-1 or NPD1) (Mukherjee et al. 2004) and 7,17S-dihydroperoxy-DHA (Butovich et al.”
A Role for the Mouse 12/15-Lipoxygenase Pathway in Promoting Epithelial Wound Healing and Host Defense
Gronert, K., Maheshwari, N., Khan, N. A., Hassan, I., Dunn, M. W., & Schwartzman, M. L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410638200 · Cited by 308 · see citing works
Oxidative stress and diabetes mellitus
Yang, H., Jin, X., Lam, C. W. K., & Yan, S.-K. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.250 · Cited by 309 · see citing works
Resolvins and protectins: mediating solutions to inflammation
Kohli, P., & Levy, B. D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00290.x · Cited by 293 · see citing works
“In this disorder, levels of DHA, NPD1 and 15-LOX are selectively decreased in the hippocampus, providing a plausible mechanism for decreased neuroprotection in Alzheimer’s disease; that being less inhibition of apoptosis and subsequently, increased neuronal cell death (Marcheselli et al., 2003; Mukherjee et al., 2004;…”
Influential
Transcriptomic analyses of murine resolution-phase macrophages
Stables, M. J., Shah, S. H., Camon, E. B., Lovering, R. C., Newson, J., Byström, J., Farrow, S. N., & Gilroy, D. W. (2011) · Blood · doi:10.1182/blood-2011-04-345330 · Cited by 293 · see citing works
DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation
Duvall, M. G., & Levy, B. D. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.11.001 · Cited by 287 · see citing works
“Protectin D1 is active in human retinal pigment epithelial cells to protect against oxidative stress-induced apoptosis (Mukherjee et al., 2004) and in glial cells to block cytokine production (Hong et al., 2003).”
The Relationship of Dietary Lipid Intake and Age-Related Macular Degeneration in a Case-Control Study: AREDS Report No. 20
(2007) · Archives of Ophthalmology · doi:10.1001/archopht.125.5.671 · Cited by 283 · see citing works
“08) 1 medium serving/wk 69 (11) 134 (12) 0.”
Identification of a Lipase-linked Cell Membrane Receptor for Pigment Epithelium-derived Factor
Notari, L., Baladrón, V., Aroca‐Aguilar, J., Balko, N., Heredia, R. J., Meyer, C., Notario, P. M., Saravanamuthu, S. S., Nueda, M., Sánchez‐Sánchez, F., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600353200 · Cited by 283 · see citing works
Polyunsaturated fatty acids in the central nervous system: evolution of concepts and nutritional implications throughout life
Alessandri, J., Guesnet, P., Vancassel, S., Astorg, P., Denis, I., Goustard, B., Aïd, S., Poumès‐Ballihaut, C., Champeil‐Potokar, G., & Lavialle, M. (2004) · annales de biologie animale biochimie biophysique · doi:10.1051/rnd:2004063 · Cited by 283 · see citing works
“Very recently, they have shown that the 10,17S-docosatriene molecule, so called “neuroprotectin D1” (NPD1), is synthesised by human retinal pigment epithelial cells treated with a calcium ionophore or with DHA [109].”
Novel Anti-Inflammatory-Pro-Resolving Mediators and Their Receptors
Serhan, C. N., Krishnamoorthy, S., Recchiuti, A., & Chiang, N. (2011) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026611109060629 · Cited by 278 · see citing works
DOCOSAHEXAENOIC ACID, FATTY ACID–INTERACTING PROTEINS, AND NEURONAL FUNCTION: Breastmilk and Fish Are Good for You
Marszalek, J. R., & Lodish, H. F. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.120624 · Cited by 270 · see citing works
Omega-3 fatty acids and their lipid mediators: Towards an understanding of resolvin and protectin formation
Weylandt, K. H., Chiu, C., Gomolka, B., Waechter, S. F., & Wiedenmann, B. J. (2012) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2012.01.005 · Cited by 259 · see citing works
Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease
Bazan, N. G. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800068-jlr200 · Cited by 256 · see citing works
Differential immunomodulation with long-chainn-3 PUFA in health and chronic disease
Sijben, J., & Calder, P. C. (2007) · Proceedings of The Nutrition Society · doi:10.1017/s0029665107005472 · Cited by 249 · see citing works
“…mediators D-series resolvins, docosatrienes and neuroprotectins, also produced by cyclooxygenase-2 and lipoxygenase under some conditions, have been identified that also appear to be antiinflammatory and inflammation resolving (Hong et al. 2003; Marcheselli et al. 2003; Mukherjee et al. 2004).”
The Docosatriene Protectin D1 Is Produced by TH2 Skewing and Promotes Human T Cell Apoptosis via Lipid Raft Clustering
Ariel, A., Li, P., Wang, W., Tang, W.-X., Fredman, G., Hong, S., Gotlinger, K. H., & Serhan, C. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509796200 · Cited by 247 · see citing works
The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Epidemiology
Dumbleton, K., Caffery, B. E., Doğru, M., Hickson-Curran, S. B., Kern, J. R., Kojima, T., Morgan, P. B., Purslow, C., Robertson, D. M., & Nelson, J. D. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13125 · Cited by 245 · see citing works
Fetal Inflammatory Response and Brain Injury in the Preterm Newborn
Malaeb, S. N., & Dammann, O. (2009) · Journal of Child Neurology · doi:10.1177/0883073809338066 · Cited by 245 · see citing works
“Neuroprotectin D1 (NPD1) is a messenger with antiapoptotic properties that can inhibit upstream signaling of the apoptotic cascade.(104) Interleukin-1-b enhances neuroprotectin D1 synthesis(105) and may offer cytoprotection to cells adjacent to the site of ongoing neuroinflammation.”
Dietary n‐3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease
Calon, F., Lim, G. P., Morihara, T., Yang, F., Ubeda, O. J., Salem, N., Frautschy, S. A., & Cole, G. M. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04253.x · Cited by 244 · see citing works
“DHA-mediated reduction of the levels of Bad such as we report here has been observed in vitro as a direct effect of neuroprotective enzymatic metabolites of DHA (Mukherjee et al., 2004).”
Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection
Bazan, N. G. (2007) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32802b7030 · Cited by 244 · see citing works
Resolving TRPV1- and TNF-α-Mediated Spinal Cord Synaptic Plasticity and Inflammatory Pain with Neuroprotectin D1
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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 › 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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