ABSTRACT
Oxysterols are derivatives of cholesterol that contain additional oxygen atoms either on the steroid nucleus or the side chains. When cells are inhibited by 25-hydroxycholesterol, a considerable interval occurs before they begin to die. During this 24 to 48 h “window”, they appear normal, gradually arresting in the G1 phase of the cell cycle. Cholesterol synthesis, however, is reduced quite rapidly, as hydroxymethylglutaryl coenzyme A reductase is dramatically reduced within the first few hours following administration of the oxysterol. The data show that oxysterols do in fact lower c-myc levels. By 24 h after addition of oxysterol, c-myc levels have been significantly reduced. Again, this downregulation does not occur in oxysterol-resistant clones. Myc is not known to function in cholesterol synthesis and, therefore, it represents a particularly intriguing gene for further study in the context of oxysterol regulation of a apoptosis.
