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Cavit Agca, Christian Grimm; Hydrogen Peroxide Influences Lif mRNA Turnover In Muller Cells In Vitro. Invest. Ophthalmol. Vis. Sci. 2011;52(14):12.
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Leukemia inhibitory factor (LIF) has been shown to be specifically expressed in Muller cells in response to photoreceptor injury and to be a key mediator of photoreceptor survival. Inhibition of LIF signaling severely accelerates retinal degeneration. Targeting Lif expression should thus have an effect on photoreceptor survival during retinal degeneration. Therefore, we elucidated the factors that affect Lif expression both at the transcriptional and post-transcriptional level in a rat Muller cell line (rMC-1).
The rMC-1 cells were treated with hydrogen peroxide (H2O2) in a time and dose dependent manner, with recombinant TNF-alpha and with an inhibitor of P38 MAPK (SB-239063). H2O2 treatment was also done in combination with actinomycinD to inhibit transcription or with serum deprivation. Treated rMC-1 cells were collected and Lif transcript levels were determined by real time PCR.
rMC-1 cells continuously expressed Lif mRNA. Both inhibition of transcription by actinomycinD and serum deprivation led to a rapid elimination of Lif transcripts from rMC-1 cells. Similarly, inhibition of P38 MAPK activity significantly reduced Lif transcript levels. Addition of H2O2 to actinomycinD treated cells or to serum deprived cells, however, inhibited the elimination of Lif mRNA by increasing Lif mRNA stability. Moreover, treatment of rMC-1 cells with recombinant TNF-alpha strongly upregulated Lif transcription.
These results strongly argue that H2O2 upregulates Lif mRNA levels through increasing the mRNA stability. Since H2O2 is a reactive oxygen species (ROS) and is known to be involved in diverse physiological responses, these data also give insights into the puzzling connection between generation of ROS and induction of survival pathways in the retina.
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