Current opinion in lipidology · 2007
Oxysterols: functional significance in fetal development and the maintenance of normal retinal function.
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Javitt Norman B
Аннотация
PURPOSE OF REVIEW: Recent findings extend the biologic activities of oxysterols as ligands for nuclear receptors to a role in morphogenesis during fetal development and to a role in the metabolism of photooxidation products of cholesterol in the retina.
RECENT FINDINGS: A 1000-fold increase of the 27-hydroxy metabolite of 7-dehydrocholesterol in the plasma of children with Smith-Lemli-Opitz syndrome imply that intermediates in cholesterol synthesis follow alternate pathways of metabolism that generate novel oxysterols. A mouse model also finds an increase in sterol intermediates as the proximate cause of dysmorphisms. A role for oxysterols in the effects of Sonic hedgehog protein focuses on their role in normal fetal development. Both CYP27A1 and CYP46A1 are expressed in primate retina indicating that local metabolism of 7-ketocholesterol to nontoxic derivatives is important for preventing retinal degeneration.
SUMMARY: Recent data expand the functional roles of oxysterols to fetal development and to the detoxification of oxidation products of cholesterol. This review shifts the focus of attention from studies of their ligand-binding activity to studies of animal models that indicate a number of important biologic effects during fetal development and during the aging process.
RECENT FINDINGS: A 1000-fold increase of the 27-hydroxy metabolite of 7-dehydrocholesterol in the plasma of children with Smith-Lemli-Opitz syndrome imply that intermediates in cholesterol synthesis follow alternate pathways of metabolism that generate novel oxysterols. A mouse model also finds an increase in sterol intermediates as the proximate cause of dysmorphisms. A role for oxysterols in the effects of Sonic hedgehog protein focuses on their role in normal fetal development. Both CYP27A1 and CYP46A1 are expressed in primate retina indicating that local metabolism of 7-ketocholesterol to nontoxic derivatives is important for preventing retinal degeneration.
SUMMARY: Recent data expand the functional roles of oxysterols to fetal development and to the detoxification of oxidation products of cholesterol. This review shifts the focus of attention from studies of their ligand-binding activity to studies of animal models that indicate a number of important biologic effects during fetal development and during the aging process.