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

Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Jul;1866(7):158927. doi: 10.1016/j.bbalip.2021.158927. Epub 2021 Mar 24.

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.

Keywords: Age-related macular degeneration; Cholesterol efflux; Oxidized low density lipoprotein; Retinal pigment epithelial cells; STARD3.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Cholesterol / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Inflammation* / genetics
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Lipoproteins, LDL* / metabolism
  • Macular Degeneration / genetics
  • Macular Degeneration / metabolism
  • Macular Degeneration / pathology
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress*
  • Retinal Pigment Epithelium* / metabolism
  • Retinal Pigment Epithelium* / pathology

Substances

  • oxidized low density lipoprotein
  • Lipoproteins, LDL
  • Cholesterol
  • Carrier Proteins
  • STARD3 protein, human
  • Membrane Proteins