Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells

Mohammad Almarhoun, Lincoln Biswas, Reem Hasaballah Alhasani, Aileen Wong, Gabriel Mbuta Tchivelekete, Xinzhi Zhou, Steven Patterson, Chris Bartholomew, Xinhua Shu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Age-related macular degeneration (AMD) is the most common cause of visual disorder in aged people and may lead to complete blindness with ageing. The major clinical feature of AMD is the presence of cholesterol enriched deposits underneath the retinal pigment epithelium (RPE) cells. The deposits can induce oxidative stress and inflammation. It has been suggested that abnormal cholesterol homeostasis contributes to the pathogenesis of AMD. However, the functional role of defective cholesterol homeostasis in AMD remains elusive. STARD proteins are a family of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. There are fifteen STARD proteins in mammals and some, such as STARD3, are responsible for cholesterol trafficking. Previously there was no study of STARD proteins in retinal cholesterol metabolism and trafficking. Here we examined expression of the Stard3 gene in mouse retinal and RPE cells at ages of 2 and 20 months. We found that expression of Stard 3 gene transcripts in both mouse RPE and retina was significantly decreased at age of 20 months when compared to that of age 2 months old. We created a stable ARPE-19 cell line overexpressing STARD3 and found this resulted in increased cholesterol efflux, reduced accumulation of intracellular oxidized LDL, increased antioxidant capacity and lower levels of inflammatory cytokines. The data suggested that STARD3 is a potential target for AMD through promoting the removal of intracellular cholesterol and slowing the disease progression.
Original languageEnglish
Article number158927
Pages (from-to)1-10
Number of pages10
JournalBiochimica et Biophysica Acta (BBA) ‐ Molecular and Cell Biology of Lipids
Volume1866
Issue number7
Early online date24 Mar 2021
DOIs
Publication statusPublished - Jul 2021

Keywords

  • age-related macular degeneration
  • STARD3
  • retinal pigment epithelial cells
  • cholesterol efflux
  • oxidized low density lipoprotein

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