25-Hydroxycholesterol cytotoxicity effect

Maguire L, Konoplyannikov M, Lord A, Maguire AR, O Brien NM (2003) Comparison of the cytotoxic effects of P-sitosterol oxides and a cholesterol oxide, 7P-hydroxycholesterol, in cultured mammalian cells. Br J Nutr 90(4) 767-775. doi 10.1079/BJN2003956... 

The toxic effect of 7-oxysterols, 25- and 27-hydroxycholesterols and their involvement in LDL cytotoxicity have been extensively studied on the different vascular cell types (Lizard et al, 1999 Aupeix et al, 1995 Clare et al, 1995 Ramasamy et al, 1992). 7a and 7p-hydroxycholesterols, 7-ketocholesterol, 25 and 27-hydroxycholesterol induce apoptosis (Brown and Jessup, 1999 Lizard et al, 1999, 1998 Zhang et al, 1997 Hughes et al, 1994). 7p-hydroperoxycholesterol is one of the most toxic Oxysterols present in oxidized LDL (Brown and Jessup, 1999 Colles et al, 1996). 25-hydroxycholesterol, though less active (Aupeix et al 1995), is able to trigger a cytochrome c release and subsequent caspase activation in CHO cells, but also calcium inaease in relation with apoptosis (Rusinol et al, 2000). 

A. Kupferberg, G. Teller, P. Behr, C. Leray, P.F. Urban and G. Vincendon, Effect of 7p-hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines cytotoxicity and metabolism, Biochim. Biophys. Acta 1013 (1989)231-238. 

The presence of an additional hydroxyl group added to the one at the 3B position can have profound effects. Oxysterols as 7-ketocholesterol, 7B-hydroxycholesterol, 7a-hydroxycholesterol and 25-hydroxycholesterol are readily formed when cholesterol is exposed to air, heat and radiation. Known physiological consequenses of oxysterols are decrease of cholesterol synthesis, effects on cell morphology and membrane associated functions and cytotoxicity towards smooth muscle cells and microorganisms. 

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