ArticleThe Journal of biological chemistry2010
Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Article
- The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases.Current neuropharmacology · 2025Review
- (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Biotransformation of docosahexaenoic acid into 10R,17S-dihydroxydocosahexaenoic acid as protectin DX 10-epimer by serial reactions of arachidonate 8R- and 15S-lipoxygenases.World journal of microbiology & biotechnology · 2024Article
- Novel lipid mediator 7Frontiers in cell and developmental biology · 2024Article
- Identification of Resolvin D1 and Protectin D1 as Potential Therapeutic Agents for Treating Kidney Stones.Oxidative medicine and cellular longevity · 2022Article
- A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2021Article
- Increased Antioxidant Capacity and Pro-Homeostatic Lipid Mediators in Ocular Hypertension-A Human Experimental Model.Journal of clinical medicine · 2020Article
- Dual Switch Mechanism of Erythropoietin as an Antiapoptotic and Pro-Angiogenic Determinant in the Retina.ACS omega · 2020Article
- Review
- Proresolving Lipid Mediators: Endogenous Modulators of Oxidative Stress.Oxidative medicine and cellular longevity · 2019Review
- Nutritional Regulators of Bcl-xL in the Brain.Molecules (Basel, Switzerland) · 2018Review
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Retinal Pigment Epithelium and Photoreceptor Preconditioning Protection Requires Docosanoid Signaling.Cellular and molecular neurobiology · 2018Article
- Improvement of Storage Medium for Cultured Human Retinal Pigment Epithelial Cells Using Factorial Design.Scientific reports · 2018Article
- The role of pro-resolving lipid mediators in ocular diseases.Molecular aspects of medicine · 2017Review
- Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection.The Journal of biological chemistry · 2017Review
- Elovanoids are novel cell-specific lipid mediators necessary for neuroprotective signaling for photoreceptor cell integrity.Scientific reports · 2017Article
- Enriched Endogenous Omega-3 Fatty Acids in Mice Ameliorate Parenchymal Cell Death After Traumatic Brain Injury.Molecular neurobiology · 2017Article
- Autophagy and KRT8/keratin 8 protect degeneration of retinal pigment epithelium under oxidative stress.Autophagy · 2017Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Retinal pigment epithelial (RPE) cell integrity is critical for the survival of photoreceptor cells. Bcl-x(L) is a major anti-apoptotic Bcl-2 protein required for RPE cell survival, and phosphorylation of Bcl-x(L) at residue Ser-62 renders this protein pro-apoptotic. In this study, we identify serine/threonine protein phosphatase 2A (PP2A) as a key regulator of Bcl-x(L) phosphorylation at residue Ser-62 in ARPE-19 cells, a spontaneously arising RPE cell line in which Bcl-x(L) is highly expressed. We found that either PP2A inhibitor okadaic acid or depletion of catalytic subunit alpha of PP2A (PP2A/Calpha) by small interfering RNA enhanced Bcl-x(L) phosphorylation when activated with hydrogen peroxide and tumor necrosis factor alpha-induced oxidative stress. Disruption of PP2A/Calpha exacerbated oxidative stress-induced apoptosis. PP2A/Calpha colocalized and interacted with S62Bcl-x(L) in cells stressed with H(2)O(2)/tumor necrosis factor alpha. By contrast, the omega-3 fatty acid docosahexaenoic acid derivative, neuroprotectin D1 (NPD1), a potent activator of survival signaling, down-regulated oxidative stress-induced phosphorylation of Bcl-x(L) by increasing protein phosphatase activity. NPD1 also attenuated the oxidative stress-induced apoptosis by knockdown of PP2A/Calpha and increased the association of PP2A/Calpha with S62Bcl-x(L) as well as total Bcl-x(L). NPD1 also enhanced the heterodimerization of Bcl-x(L) with its counterpart, pro-apoptotic protein Bax. Thus, NPD1 modulates the activation of this Bcl-2 family protein by dephosphorylating in a PP2A-dependent manner, suggesting a coordinated, NPD1-mediated regulation of cell survival in response to oxidative stress.
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Registered trials
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