Cytotoxic effects of oxysterols produced during ozonolysis of cholesterol in murine GT1-7 hypothalamic neurons

K. Sathishkumar, Subramanyam N. Murthy, Rao M. Uppu

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Ozone present in the photochemical smog or generated at the inflammatory sites is known to oxidize cholesterol and its 3-acyl esters. The oxidation results in the formation of multiple "ozone-specific" oxysterols, some of which are known to cause abnormalities in the metabolism of cholesterol and exert cytotoxicity. The ozone-specific oxysterols have been shown to favor the formation of atherosclerotic plaques and amyloid fibrils involving pro-oxidant processes. In the present communication, cultured murine GT1-7 hypothalamic neurons were studied in the context of cholesterol metabolism, formation of reactive oxygen species, intracellular Ca2+ levels and cytotoxicity using two most commonly occurring cholesterol ozonolysis products, 3β- hydroxy-5-oxo-5,6-secocholestan-6-al (ChSeco) and 5β, 6β-epoxy-cholesterol (ChEpo). It was found that ChSeco elicited cytotoxicity at lower concentration (IC50 = 21 ± 2.4 μM) than did ChEpo (IC50 = 43 ± 3.7 μM). When tested at their IC50 concentrations in GT1-7 cells, both ChSeco and ChEpo resulted in the generation of ROS, the magnitude of which was comparable. N-acetyl-l-cysteine and Trolox attenuated the cytotoxic effects of ChSeco and ChEpo. The intracellular Ca2+ levels were not altered by either ChSeco or ChEpo. Methyl-β-cyclodextrins, which cause depletion of cellular cholesterol, prevented ChSeco- but not ChEpo-induced cytotoxicity. The cell death caused by ChEpo, but not ChSeco, was prevented by exogenous cholesterol. Although oxidative stress plays a significant role, the results of the present study indicate differences in the pathways of cell death induced by ChSeco and ChEpo in murine GT1-7 hypothalamic neurons.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalFree Radical Research
Volume41
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Fingerprint

Neurons
Cholesterol
Cytotoxicity
Ozone
Inhibitory Concentration 50
3-hydroxy-5-oxo-5,6-secocholestan-6-al
Oxysterols
Cell death
Metabolism
Reactive Oxygen Species
Cell Death
Smog
Acetylcysteine
Oxidative stress
Cyclodextrins
Atherosclerotic Plaques
Amyloid
Cysteine
Esters
Oxidative Stress

Keywords

  • Cholesterol
  • Cytotoxicity
  • Neuronal cells
  • Oxysterols
  • Ozone
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cytotoxic effects of oxysterols produced during ozonolysis of cholesterol in murine GT1-7 hypothalamic neurons. / Sathishkumar, K.; Murthy, Subramanyam N.; Uppu, Rao M.

In: Free Radical Research, Vol. 41, No. 1, 01.2007, p. 82-88.

Research output: Contribution to journalArticle

Sathishkumar, K. ; Murthy, Subramanyam N. ; Uppu, Rao M. / Cytotoxic effects of oxysterols produced during ozonolysis of cholesterol in murine GT1-7 hypothalamic neurons. In: Free Radical Research. 2007 ; Vol. 41, No. 1. pp. 82-88.
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