The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication.
Fiche publication
Date publication
janvier 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FOURNEL-GIGLEUX Sylvie, Pr MAGDALOU Jacques, Dr OUZZINE Mohamed
Tous les auteurs :
Ouzzine M, Gulberti S, Ramalanjaona N, Magdalou J, Fournel-Gigleux S
Lien Pubmed
Résumé
UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of beta-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-alpha-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.
Référence
Front Cell Neurosci. 2014 Oct 28;8:349