Abstract:
Oxysterols are the 27-carbon products of cholesterol oxidation by both enzymic and non-enzymic
mechanisms. Their roles in cholesterol homeostasis, as well as in diseases in which oxidative
damage and lipid peroxidation are implicated (e.g. atherosclerosis), have been investigated
extensively. However, there are a number of important considerations regarding the physiological/
pathophysiological functions and activities of the different oxysterols. First, in both normal and
diseased tissues, the levels of oxysterols are very low when compared to the native sterol. Also,
when assessing studies that have measured the levels of oxysterols in biological samples, there must
be careful consideration as to the method of sample isolation, storage and sampling. This is because
of the potential generation or loss of oxysterols during these procedures. Additionally, the relevance
of in vitro studies which examine the effects of oxysterols upon cell function should be judged as to
cellular oxysterol content (both in terms of the levels of oxysterol and the degree of esterification)
resulting from the oxysterol treatment. We present evidence that the means by which oxysterol is
delivered in vitro determines whether the oxysterol content reflects what has been found in vivo.
Studies identifying the specific cellular targets of oxysterol indicate that several oxysterols may be
regulators of cellular lipid metabolism via control of gene transcription.
