Cholesterol is more susceptible to oxidation than linoleates in cultured cells under oxidative stress induced by selenium deficiency and free radicals

Polyunsaturated fatty acids and their esters are known to be susceptible to free-radical mediated oxidation, while cholesterol is more resistant to oxidation. The present study focused on the relative susceptibilities of linoleates and cholesterol in Jurkat cells under oxidative stress induced by selenium deficiency and free radical insult, as assessed by total hydroxyoctadecadienoic acids (tHODE) and total 7-hydroxycholesterol (t7-OHCh) measured after reduction and saponification. It was observed that the levels of tHODE and t7-OHCh significantly increased by both oxidative insults. The increased amounts of t7-OHCh were higher than those of tHODE in both selenium-deficient and free radical-treated cells. These results suggest that, in contrast to plasma oxidation where cholesterol is much more resistant to oxidation than linoleates, cellular cholesterol is more susceptible to oxidation than cellular linoleates.     

7-Hydroxycholestrol as a possible biomarker of cellular lipid peroxidation: Difference between cellular and plasma lipid peroxidation

Polyunsaturated fatty acids and their esters are known to be susceptible to free radical-mediated oxidation, whereas cholesterol is thought to be more resistant to oxidation. In fact, it has been observed that in the case of plasma lipid peroxidation, the amount of oxidation products of polyunsaturated fatty acids such as linoleic acid was higher than that of cholesterol. In contrast, during oxidative stress-induced cellular lipid peroxidation, oxidation products of cholesterol such as 7-hydroxycholesterol (7-OHCh) were detected in greater amounts than those of linoleates such as hydroxyoctadecadienoic acid (HODE). There are several forms of oxidation products of cholesterol and linoleates in vivo, namely, hydroperoxides, as well as the hydroxides of both the free and ester forms of cholesterol and linoleates. To evaluate these oxidation products, a method used to determine the lipid oxidation products after reduction and saponification was developed. With this method, several forms of oxidation products of cholesterol and linoleates are measured as total 7-OHCh (t7-OHCh) and total HODE (tHODE), respectively. During free radical-mediated lipid peroxidation in plasma, the amount of tHODE was 6.3-fold higher than that of t7-OHCh. In contrast, when Jurkat cells were exposed to free radicals, the increased amount of cellular t7-OHCh was 5.7-fold higher than that of tHODE. Higher levels of t7-OHCh than those of tHODE have also been observed in selenium-deficient Jurkat cells and glutamate-treated neuronal cells. These results suggest that, in contrast to plasma oxidation, cellular cholesterol is more susceptible to oxidation than cellular linoleates. Collectively, cholesterol oxidation products at the 7-position may be a biomarker of cellular lipid peroxidation.