24S-hydroxycholesterol induces inflammatory gene expression in primary human neural cells.
24S-hydroxycholesterol, the primary oxidation product of cholesterol in the brain, plays a key role in cholesterol elimination and homeostasis. While the concentration of this neurotoxic oxysterol decreases with age, 24S-hydroxycholesterol is elevated in Alzheimer's disease. In this study, we examined the effects of 24S-hydroxycholesterol on gene expression in human neural cells, a primary coculture of neurons and glia useful for studying pathogenic mechanisms in Alzheimer's disease. DNA array and Western analysis revealed elevations in the expression of a pro-inflammatory gene family that included beta-amyloid precursor protein, cyclooxygenase-2, cytosolic phospholipase A2 and heat shock protein 70, an effect that was partially suppressed by simvastatin. These data indicate that cholesterol oxides induce atypical gene expression in neural cells that may contribute to the etiology or pathogenesis of inflammatory brain disease.
Alexandrov
Piotr
P
Russian Academy of Medical Sciences, Moscow 113152, Russia.
Cui
Jian-Guo
JG
Zhao
Yuhai
Y
Lukiw
Walter J
WJ
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D002784:Cholesterol / Q000494:pharmacology; D051546:Cyclooxygenase 2; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; D006888:Hydroxycholesterols; D008565:Membrane Proteins; D014404:Tubulin; C044563:24-hydroxycholesterol; D002784:Cholesterol; D019821:Simvastatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2