Regulation of alpha-synuclein expression by liver X receptor ligands in vitro.
Alpha-synuclein is a lipid-binding protein expressed in neurons and oligodendrocytes which is increased in Parkinson's disease. We identified two putative liver X receptor (LXR) response elements in the human alpha-synuclein gene and used synthetic (TO901317, GW3695) and physiological (27-hydroxycholesterol) LXR activators to assess regulation of alpha-synuclein. LXR ligands upregulated alpha-synuclein mRNA by two-five-fold in human SK-N-SH neurons and three-six-fold in human MO3.13 oligodendrocytes. Significant 50% to four-fold induction of alpha-synuclein protein was also detected. Under these conditions, mRNA for LXR-responsive gene ABCA1 was significantly upregulated 15-40-fold and 5-25-fold in neurons and oligodendrocytes, respectively. LXR may, therefore, contribute to the regulation of alpha-synuclein expression in neurons and oligodendrocytes.
Prince of Wales Medical Research Institute, Sydney, Randwick, New South Wales, Australia.
Danni
D
Cheng
Woojin Scott
WS
Kim
Brett
B
Garner
D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D000071518:Liver X Receptors; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D006888:Hydroxycholesterols; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; D051844:alpha-Synuclein; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides; C076996:27-hydroxycholesterol