Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and α-synuclein in human neuroblastoma SH-SY5Y cells

Jaya Prasanthi Rantham Prabhakara, Gwen Feist, Sarah Thomasson, Alex Thompson, Eric Schommer, Othman Ghribi

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Evidence suggests that environmental and dietary factors may contribute to the pathogenesis of Parkinson's disease (PD). High dietary intake of cholesterol is such a factor that has been shown to increase or decrease the risk of PD. However, because circulating cholesterol does not cross the blood-brain barrier, the mechanisms linking dietary cholesterol to the pathogenesis of PD remain to be understood. In contrast to cholesterol, the oxidized cholesterol metabolites (oxysterols), 24S-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), can cross the blood-brain barrier and may place the brain at risk of degeneration. In this study, we incubated the human neuroblastoma SH-SY5Y cells for 24 h with 24-OHC, 27-OHC, or a mixture of 24-OHC plus 27-OHC, and have determined effects on tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis) levels, α-synuclein levels, and apoptosis. We demonstrate that while 24-OHC increases the levels of tyrosine hydroxylase, 27-OHC increases levels of α-synuclein, and induces apoptosis. Our findings show for the first time that oxysterols trigger changes in levels of proteins that are associated with the pathogenesis of PD. As steady state levels of 24-OHC and 27-OHC are tightly regulated in the brain, disturbances in these levels may contribute to the pathogenesis of PD.

Original languageEnglish (US)
Pages (from-to)1722-1729
Number of pages8
JournalJournal of Neurochemistry
Volume107
Issue number6
DOIs
StatePublished - Dec 1 2008

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Synucleins
Tyrosine 3-Monooxygenase
Neuroblastoma
Parkinson Disease
Dietary Cholesterol
Cholesterol
Blood-Brain Barrier
Brain
Apoptosis
Metabolites
Dopamine
27-hydroxycholesterol
24-hydroxycholesterol
Enzymes
Proteins

Keywords

  • 24-hydroxycholesterol
  • 27-hydroxycholesterol
  • Apoptosis
  • Oxysterols
  • Tyrosine hydroxylase
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and α-synuclein in human neuroblastoma SH-SY5Y cells. / Rantham Prabhakara, Jaya Prasanthi; Feist, Gwen; Thomasson, Sarah; Thompson, Alex; Schommer, Eric; Ghribi, Othman.

In: Journal of Neurochemistry, Vol. 107, No. 6, 01.12.2008, p. 1722-1729.

Research output: Contribution to journalArticle

Rantham Prabhakara, Jaya Prasanthi ; Feist, Gwen ; Thomasson, Sarah ; Thompson, Alex ; Schommer, Eric ; Ghribi, Othman. / Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on tyrosine hydroxylase and α-synuclein in human neuroblastoma SH-SY5Y cells. In: Journal of Neurochemistry. 2008 ; Vol. 107, No. 6. pp. 1722-1729.
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