Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366208093> ?p ?o ?g. }
- W4366208093 abstract "The retinal pigment epithelium (RPE) is progressively degenerated during age-related macular degeneration (AMD), one of the leading causes of irreversible blindness, which clinical hallmark is the buildup of sub-RPE extracellular material. Clinical observations indicate that Zn dyshomeostasis can initiate detrimental intracellular events in the RPE. In this study, we used a primary human fetal RPE cell culture model producing sub-RPE deposits accumulation that recapitulates features of early AMD to study Zn homeostasis and metalloproteins changes. RPE cell derived samples were collected at 10, 21 and 59 days in culture and processed for RNA sequencing, elemental mass spectrometry and the abundance and cellular localization of specific proteins. RPE cells developed processes normal to RPE, including intercellular unions formation and expression of RPE proteins. Punctate deposition of apolipoprotein E, marker of sub-RPE material accumulation, was observed from 3 weeks with profusion after 2 months in culture. Zn cytoplasmic concentrations significantly decreased 0.2 times at 59 days, from 0.264 ± 0.119 ng·μg −1 at 10 days to 0.062 ± 0.043 ng·μg −1 at 59 days ( p < 0.05). Conversely, increased levels of Cu (1.5-fold in cytoplasm, 5.0-fold in cell nuclei and membranes), Na (3.5-fold in cytoplasm, 14.0-fold in cell nuclei and membranes) and K (6.8-fold in cytoplasm) were detected after 59-days long culture. The Zn-regulating proteins metallothioneins showed significant changes in gene expression over time, with a potent down-regulation at RNA and protein level of the most abundant isoform in primary RPE cells, from 0.141 ± 0.016 ng·mL −1 at 10 days to 0.056 ± 0.023 ng·mL −1 at 59 days (0.4-fold change, p < 0.05). Zn influx and efflux transporters were also deregulated, along with an increase in oxidative stress and alterations in the expression of antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase. The RPE cell model producing early accumulation of extracellular deposits provided evidences on an altered Zn homeostasis, exacerbated by changes in cytosolic Zn-binding proteins and Zn transporters, along with variations in other metals and metalloproteins, suggesting a potential role of altered Zn homeostasis during AMD development." @default.
- W4366208093 created "2023-04-19" @default.
- W4366208093 creator A5014478440 @default.
- W4366208093 creator A5019297305 @default.
- W4366208093 creator A5022319849 @default.
- W4366208093 creator A5033850868 @default.
- W4366208093 creator A5044252919 @default.
- W4366208093 creator A5044550111 @default.
- W4366208093 creator A5087430277 @default.
- W4366208093 date "2023-04-17" @default.
- W4366208093 modified "2023-10-16" @default.
- W4366208093 title "Altered zinc homeostasis in a primary cell culture model of the retinal pigment epithelium" @default.
- W4366208093 cites W114316392 @default.
- W4366208093 cites W1438640379 @default.
- W4366208093 cites W1785652742 @default.
- W4366208093 cites W1973207504 @default.
- W4366208093 cites W1978391747 @default.
- W4366208093 cites W1978437552 @default.
- W4366208093 cites W1984271994 @default.
- W4366208093 cites W1984659998 @default.
- W4366208093 cites W1992706834 @default.
- W4366208093 cites W1996103543 @default.
- W4366208093 cites W1998593109 @default.
- W4366208093 cites W1998991620 @default.
- W4366208093 cites W1999574084 @default.
- W4366208093 cites W2001720244 @default.
- W4366208093 cites W2004603626 @default.
- W4366208093 cites W2009738449 @default.
- W4366208093 cites W2009960960 @default.
- W4366208093 cites W2016520383 @default.
- W4366208093 cites W2020391754 @default.
- W4366208093 cites W2021163002 @default.
- W4366208093 cites W2026329770 @default.
- W4366208093 cites W2029422501 @default.
- W4366208093 cites W2035918997 @default.
- W4366208093 cites W2036663456 @default.
- W4366208093 cites W2039988441 @default.
- W4366208093 cites W2048824833 @default.
- W4366208093 cites W2053108757 @default.
- W4366208093 cites W2055720749 @default.
- W4366208093 cites W2057266930 @default.
- W4366208093 cites W2060764677 @default.
- W4366208093 cites W2061731519 @default.
- W4366208093 cites W2078471699 @default.
- W4366208093 cites W2088791095 @default.
- W4366208093 cites W2098193566 @default.
- W4366208093 cites W2100762672 @default.
- W4366208093 cites W2102278945 @default.
- W4366208093 cites W2103472715 @default.
- W4366208093 cites W2111274886 @default.
- W4366208093 cites W2112310296 @default.
- W4366208093 cites W2114914263 @default.
- W4366208093 cites W2120148313 @default.
- W4366208093 cites W2122658884 @default.
- W4366208093 cites W2123230988 @default.
- W4366208093 cites W2130775876 @default.
- W4366208093 cites W2132471916 @default.
- W4366208093 cites W2136501493 @default.
- W4366208093 cites W2141588316 @default.
- W4366208093 cites W2154703818 @default.
- W4366208093 cites W2179438025 @default.
- W4366208093 cites W2330453389 @default.
- W4366208093 cites W2520110281 @default.
- W4366208093 cites W2528637216 @default.
- W4366208093 cites W2566154985 @default.
- W4366208093 cites W2576430281 @default.
- W4366208093 cites W2584917966 @default.
- W4366208093 cites W2740863379 @default.
- W4366208093 cites W2761604622 @default.
- W4366208093 cites W2774072836 @default.
- W4366208093 cites W2793534505 @default.
- W4366208093 cites W2896707534 @default.
- W4366208093 cites W2898580429 @default.
- W4366208093 cites W2905434803 @default.
- W4366208093 cites W2944525985 @default.
- W4366208093 cites W2972368830 @default.
- W4366208093 cites W2991518215 @default.
- W4366208093 cites W3028513630 @default.
- W4366208093 cites W3092175833 @default.
- W4366208093 cites W3105075054 @default.
- W4366208093 cites W3108197638 @default.
- W4366208093 cites W3119618794 @default.
- W4366208093 cites W3134017539 @default.
- W4366208093 cites W3213759958 @default.
- W4366208093 cites W4211068092 @default.
- W4366208093 doi "https://doi.org/10.3389/fnut.2023.1124987" @default.
- W4366208093 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37139441" @default.
- W4366208093 hasPublicationYear "2023" @default.
- W4366208093 type Work @default.
- W4366208093 citedByCount "1" @default.
- W4366208093 countsByYear W43662080932023 @default.
- W4366208093 crossrefType "journal-article" @default.
- W4366208093 hasAuthorship W4366208093A5014478440 @default.
- W4366208093 hasAuthorship W4366208093A5019297305 @default.
- W4366208093 hasAuthorship W4366208093A5022319849 @default.
- W4366208093 hasAuthorship W4366208093A5033850868 @default.
- W4366208093 hasAuthorship W4366208093A5044252919 @default.
- W4366208093 hasAuthorship W4366208093A5044550111 @default.
- W4366208093 hasAuthorship W4366208093A5087430277 @default.
- W4366208093 hasBestOaLocation W43662080931 @default.