Deletion of TSPO resulted in change of metabolomic profile in retinal pigment epithelial cells

Abdulwahab Alamri, Lincoln Biswas, David G. Watson, Xinhua Shu

Research output: Contribution to journalArticle

Abstract

Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD.

LanguageEnglish
Article number1387
Number of pages17
JournalInternational Journal of Molecular Sciences
Volume20
Issue number6
DOIs
Publication statusPublished - 19 Mar 2019

Fingerprint

deletion
Retinal Pigments
Metabolomics
pigments
Pigments
Epithelial Cells
profiles
cells
lipoproteins
Lipoproteins
Glutathione Disulfide
metabolism
Metabolism
Lipids
metabolic wastes
lipids
Glycerophospholipids
nutrition
efflux
photoreceptors

Keywords

  • age related macular degeneration
  • metabolites
  • retinal pigment epithelial cells
  • TSPO

Cite this

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title = "Deletion of TSPO resulted in change of metabolomic profile in retinal pigment epithelial cells",
abstract = "Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retinal pigment epithelial (RPE) cells, are a clinical feature of AMD and associated with AMD progression. RPE cells support photoreceptor function by providing nutrition, phagocytosing outer segments and removing metabolic waste. Dysfunction and death of RPE cells are early features of AMD. The translocator protein, TSPO, plays an important role in RPE cholesterol efflux and loss of TSPO results in increased intracellular lipid accumulation and reactive oxygen species (ROS) production. This study aimed to investigate the impact of TSPO knockout on RPE cellular metabolism by identifying the metabolic differences between wildtype and knockout RPE cells, with or without treatment with oxidized low density lipoprotein (oxLDL). Using liquid chromatography mass spectrometry (LC/MS), we differentiated several metabolic pathways among wildtype and knockout cells. Lipids amongst other intracellular metabolites were the most influenced by loss of TSPO and/or oxLDL treatment. Glucose, amino acid and nucleotide metabolism was also affected. TSPO deletion led to up-regulation of fatty acids and glycerophospholipids, which in turn possibly affected the cell membrane fluidity and stability. Higher levels of glutathione disulphide (GSSG) were found in TSPO knockout RPE cells, suggesting TSPO regulates mitochondrial-mediated oxidative stress. These data provide biochemical insights into TSPO-associated function in RPE cells and may shed light on disease mechanisms in AMD.",
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Deletion of TSPO resulted in change of metabolomic profile in retinal pigment epithelial cells. / Alamri, Abdulwahab; Biswas, Lincoln; Watson, David G.; Shu, Xinhua.

In: International Journal of Molecular Sciences, Vol. 20, No. 6, 1387, 19.03.2019.

Research output: Contribution to journalArticle

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