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

3 Downloads (Pure)

Abstract

Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retina 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 mitochondria-mediated oxidative stress. These data provide biochemical insights into TSPO-associated its function in RPE cells and may shed light on disease mechanisms in AMD.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
DOIs
Publication statusPublished - 19 Mar 2019

Fingerprint

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

Keywords

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

Cite this

@article{804d114f013d4357b0e5ce0c953ee115,
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 retina 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 mitochondria-mediated oxidative stress. These data provide biochemical insights into TSPO-associated its function in RPE cells and may shed light on disease mechanisms in AMD.",
keywords = "TSPO, metabolites, retinal pigment epithelial cells, age related macular degeneration",
author = "Abdulwahab Alamri and Lincoln Biswas and Watson, {David G.} and Xinhua Shu",
note = "Acceptance in SAN",
year = "2019",
month = "3",
day = "19",
doi = "10.3390/ijms20061387",
language = "English",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",

}

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 , 19.03.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Deletion of TSPO resulted in change of metabolomic profile in retinal pigment epithelial cells

AU - Alamri, Abdulwahab

AU - Biswas, Lincoln

AU - Watson, David G.

AU - Shu, Xinhua

N1 - Acceptance in SAN

PY - 2019/3/19

Y1 - 2019/3/19

N2 - Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retina 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 mitochondria-mediated oxidative stress. These data provide biochemical insights into TSPO-associated its function in RPE cells and may shed light on disease mechanisms in AMD.

AB - Age-related macular degeneration is the main cause of vision loss in the aged population worldwide. Drusen, extracellular lesions formed underneath the retina 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 mitochondria-mediated oxidative stress. These data provide biochemical insights into TSPO-associated its function in RPE cells and may shed light on disease mechanisms in AMD.

KW - TSPO

KW - metabolites

KW - retinal pigment epithelial cells

KW - age related macular degeneration

U2 - 10.3390/ijms20061387

DO - 10.3390/ijms20061387

M3 - Article

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

ER -