Regulated expression of apolipoprotein E by human retinal pigment epithelial cells.
In early age-related macular degeneration (AMD), lipid-containing deposits (drusen) accumulate in Bruch's membrane underlying the retinal pigment epithelium (RPE). Recent studies indicate that apolipoprotein E (apoE) may play a role in lipid trafficking in AMD. Compared with the apoE3 allele, the apoE4 and apoE2 alleles are associated with decreased and increased risk for AMD, respectively; drusen contain high levels of apoE, and apoE null mice develop lipid deposits in Bruch's membrane similar to those observed in AMD. Primary cultures of human RPE cells expressing the apoE3 allele were grown on Transwell culture plates. Western blotting, ELISA assay, and mass spectrometry confirmed that apoE3 was secreted into the apical and basal chambers and that secretion was upregulated by thyroid hormone, 9-cis-retinoic acid, and 22(R)-hydroxycholesterol. In addition, basally secreted apoE associated with exogenously added HDL. These results indicate that apoE secretion can be regulated by specific hormones and that apoE associates with HDL. The findings are consistent with a role for apoE in lipid trafficking through Bruch's membrane and may be relevant to AMD.
Ishida
Brian Y
BY
Cardiovascular Research Institute, University of California, San Francisco, CA, USA.
Bailey
Kathy R
KR
Duncan
Keith G
KG
Chalkley
Robert J
RJ
Burlingame
A L
AL
Kane
John P
JP
Schwartz
Daniel M
DM
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000235:genetics; D001692:Biological Transport / Q000502:physiology; D016570:Bruch Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D006888:Hydroxycholesterols; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012168:Retinal Pigments / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
D001057:Apolipoproteins E; D006888:Hydroxycholesterols; D008075:Lipoproteins, HDL; D012168:Retinal Pigments; D014212:Tretinoin