Early Transcriptomic Response to OxLDL in Human Retinal Pigment Epithelial Cells

Autor: Francesco Giorgianni, Diwa Koirala, Sarka Beranova-Giorgianni
Rok vydání: 2020
Předmět:
0301 basic medicine
Aging
NF-E2-Related Factor 2
retinal pigment epithelium
medicine.disease_cause
Article
Catalysis
Cell Line
lcsh:Chemistry
Inorganic Chemistry
Transcriptome
Macular Degeneration
03 medical and health sciences
0302 clinical medicine
Gene expression
medicine
Humans
oxidative stress
Macula Lutea
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Gene
Phospholipids
Spectroscopy
Retinal pigment epithelium
Chemistry
Organic Chemistry
drusen
Lipid metabolism
Cholesterol
LDL
General Medicine
Computer Science Applications
Cell biology
Lipoproteins
LDL
Cholesterol
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Receptors
Aryl Hydrocarbon
lcsh:Biology (General)
lcsh:QD1-999
oxidized LDL
030221 ophthalmology & optometry
lipids (amino acids
peptides
and proteins)
transcriptome
Oxidative stress
Intracellular
Lipoprotein
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 22
International Journal of Molecular Sciences, Vol 21, Iss 8818, p 8818 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21228818
Popis: In the sub-retinal pigment epithelium (sub-RPE) space of the aging macula, deposits of oxidized phospholipids, oxidized derivatives of cholesterol and associated oxidized low-density lipoproteins (OxLDL) are considered contributors to the onset and development of age-related macular degeneration (AMD). We investigated the gene expression response of a human-derived RPE cell line exposed for short periods of time to non-cytotoxic levels of OxLDL or LDL. In our cell model, treatment with OxLDL, but not LDL, generated an early gene expression response which affected more than 400 genes. Gene pathway analysis unveiled gene networks involved in the regulation of various cellular functions, including acute response to oxidative stress via up-regulation of antioxidative gene transcripts controlled by nuclear factor erythroid-2 related factor 2 (NRF2), and up-regulation of aryl hydrocarbon receptor-controlled detoxifying gene transcripts. In contrast, circadian rhythm-controlling genes and genes involved in lipid metabolism were strongly down-regulated. Treatment with low-density lipoprotein (LDL) did not induce the regulation of these pathways. These findings show that RPE cells are able to selectively respond to the oxidized forms of LDL via the up-regulation of gene pathways involved in molecular mechanisms that minimize cellular oxidative damage, and the down-regulation of the expression of genes that regulate the intracellular levels of lipids and lipid derivatives. The effect on genes that control the cellular circadian rhythm suggests that OxLDL might also disrupt the circadian clock-dependent phagocytic activity of the RPE. The data reveal a complex cellular response to a highly heterogeneous oxidative stress-causing agent such as OxLDL commonly present in drusen formations.
Databáze: OpenAIRE
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