The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Selective Survival Rescue in 15-Lipoxygenase-1-deficient Retinal Pigment Epithelial Cells by the Novel Docosahexaenoic Acid-derived Mediator, Neuroprotectin D1
Open accessAbstract
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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“sAPPα may activate NPD1 biosynthetic enzymes PLA2 and/or a 15-LOX– like enzyme integral to NPD1 biosynthesis (Calandria et al., 2009; Marcheselli et al., 2003).”
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 Calandria et al., 2009
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Resolvins and protectins in inflammation resolution
Serhan, C. N., & Petasis, N. A. (2011) · Chemical Reviews · doi:10.1021/cr100396c · Cited by 996
Self-citationSerhan, 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
Specialized pro-resolving lipid mediators in the inflammatory response: An update
Bannenberg, G., & Serhan, C. N. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.08.002 · Cited by 464
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Metadata
- 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.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 284
- Issue
- 26
- Pages
- 17877-17882
- ISSN
- 0021-9258 (ISSN-L)
- 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
- 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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