NPD1 induction of retinal pigment epithelial cell survival involves PI3K/Akt phosphorylation signaling.
Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes survival in cells exposed to oxidative stress by inducing the activity of anti-inflammatory mediators and suppressing the expression of pro-inflammatory genes. Though retinal pigment epithelial (RPE) cells naturally produce NPD1 from DHA, investigating the mechanisms through which exogenous NPD1 induces cell survival is essential to assess mechanisms of actions and the potential of this lipid mediator for treatment of retinal degenerative diseases. The PI3K/Akt and mTOR/p70S6K pathways are responsible for supporting cell survival upon exposure to oxidative stress. In human ARPE-19 cells pretreated with NPD1 then exposed to varying concentrations of oxidative stress or repeated exposures to oxidative stress, Akt, mTOR, and p70S6K were phosphorylated to a greater extent and for a greater duration than cells not pretreated with NPD1. In addition to increased phosphorylation, a subsequent decreased rate of apoptosis was observed upon NPD1 treatment. Thus NPD1 bioactivity in RPE cells enhances activation of these pathways and promotes cell integrity and survival.
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA.
Natalie A
NA
Halapin
Nicolas G
NG
Bazan
D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D004281:Docosahexaenoic Acids / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D004281:Docosahexaenoic Acids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C487679:protectin D1; C546842:MTOR protein, human