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Hong Wei, James T Handa; Nrf2 and Hif1a have opposite responses to oxidative stress in ARPE-19 cells.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6049.
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© ARVO (1962-2015); The Authors (2016-present)
Smoking causes oxidative stress and damage to the retina, reduces blood flow in eye tissue, and promotes ischemia, hypoxia, and micro-infarctions. It also induces cell death to retinal pigment epithelial (RPE) cells. This study explores how the RPE cell responds to stress induced by cigarette smoking and hypoxia, and how the transcription factor NF-E2-related factor 2 (Nrf2) and Hypoxia Inducible Factor 1 alpha (Hif1a), which has been reported to be induced by oxidative stress in addition to hypoxia, can influence the anti-oxidant response through JNK and p38 signaling.
ARPE-19 cells were grown to confluence, serum starved for 24h, and then treated with cigarette smoke extract (CSE) and 1% O2 for 24h. The transcription factors Nrf2 and Hif1a proteins and MAPK pathway signaling were analyzed by Western blotting.
CSE induced a significant dose dependent increase in NRF2 protein (p<0.01) and a remarkable reduction in Hif1a (p<0.001) in ARPE-19 cells, while treatment with 1% O2 resulted in a significant increase in Hif1a (p<0.01) with no change in Nrf2. Since oxidative stress and hypoxia can either induce or impair JNK or p38 signaling, we next looked at phosphorylated JNK and p38 after CSE treatment. CSE decreased phospho-JNK (p<0.01) and increased phosphor-p38 (p<0.01) compared to control treated cells while 1% O2 increased phospho-JNK (p<0.01) and decreased phospho-p38 (p<0.05).
NRF2 and Hif1a respond differently to oxidative stress in RPE cells, with differential signaling though Phospho-JNK and Phospho-p38, which can mediate inflammation, neovascularization, and apoptosis.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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