title: Bisretinoid degradation and the ubiquitin-proteasome system.
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.
authors.affiliation: Department of Ophthalmology and Cell Biology, Columbia University, 630 W. 168 Street, 10032, New York, NY, USA, jrs88@columbia.edu.
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.forename: Jilin
authors.initials: J
authors.lastname: Zhou
authors.forename: Shanti Kaligotla
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D012172:Retinaldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D008062:Lipofuscin; D012176:Retinoids; D025801:Ubiquitin; C525876:retinal dimer; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione; D012172:Retinaldehyde