Abstract
Bisretinoid fluorophores of retinal pigment epithelial (RPE) lipofuscin have been shown to undergo degradation in two ways, the first involving photofragmentation following photooxidation of their polyene structure and the second being enzyme-mediated and limited, thus far, to in vitro models employing horseradish peroxidase (HRP). Here we show that both of these processes impact the ubiquitin–proteasome system (UPS) of the RPE cell. By measuring the consumption of A2E and all-trans-retinal dimer by HPLC, we confirmed that both HRP-mediated and photodegradation of the compounds occurred and that in both cases the chymotrypsin-like and trypsin-like activities of the proteasome system were decreased. With HRP-mediated degradation of A2E, there was a small negative impact on cell viability that was not mitigated by elevating gluthathione in the cell.
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Acknowledgments
This study was supported by the Edward N. and Della L. Thome Memorial Foundation, National Institutes of Health grant P30EY019007, and a grant from Research to Prevent Blindness to the Department of Ophthalmology, Columbia University.
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Sparrow, J., Zhou, J., Ghosh, S., Liu, Z. (2014). Bisretinoid Degradation and the Ubiquitin-Proteasome System. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_75
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DOI: https://doi.org/10.1007/978-1-4614-3209-8_75
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