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 language | English (US) |
|---|---|
| Pages (from-to) | 82-88 |
| Number of pages | 7 |
| Journal | Free Radical Research |
| Volume | 41 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Cytotoxic effects of oxysterols produced during ozonolysis of cholesterol in murine GT1-7 hypothalamic neurons
AU - Sathishkumar, K.
AU - Murthy, Subramanyam N.
AU - Uppu, Rao M.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
KW - Cholesterol
KW - Cytotoxicity
KW - Neuronal cells
KW - Oxysterols
KW - Ozone
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=33845384842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845384842&partnerID=8YFLogxK
U2 - 10.1080/10715760600950566
DO - 10.1080/10715760600950566
M3 - Article
C2 - 17164181
AN - SCOPUS:33845384842
VL - 41
SP - 82
EP - 88
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 1
ER -