INTRODUCTION: Astrocytes are involved in multiple brain functions in physiological conditions. Cytochromes P450 are expressed in astrocytes and play a role in brain metabolism and in neuroprotection. BACKGROUND: Although the levels of various cytochromes P450 in brain regions are low, these enzymes were reported to be expressed at relatively high level in astroglial cells and may play a critical role in the biotransformation of endogenous or exogenous compounds. Astroglial cytochromes P450 expression suggests a putative capacity to metabolize psychoactive or lipophilic xenobiotics in situ, associated with pharmacological and/or toxicological consequences. Astrocytes appear to be the most active steroidogenic cells in the brain, expressing neurosteroïdogenic cytochromes P450 and producing various neurosteroids. Cytochrome P450 epoxygenase enzymes, which catalyze the formation of vasoactive compounds are also present in astrocytes, contributing to the regulation of the cerebral blood flow. PERSPECTIVES AND CONCLUSION: This review underlines the crucial roles of astroglial cytochromes P450 in brain functions. Identification of the molecular mechanisms involved in the regulation of these enzymes could open therapeutic perspectives and improve our understanding in neuroprotection.
INTRODUCTION: Astrocytes are involved in multiple brain functions in physiological conditions. Cytochromes P450 are expressed in astrocytes and play a role in brain metabolism and in neuroprotection. BACKGROUND: Although the levels of various cytochromes P450 in brain regions are low, these enzymes were reported to be expressed at relatively high level in astroglial cells and may play a critical role in the biotransformation of endogenous or exogenous compounds. Astroglial cytochromes P450 expression suggests a putative capacity to metabolize psychoactive or lipophilic xenobiotics in situ, associated with pharmacological and/or toxicological consequences. Astrocytes appear to be the most active steroidogenic cells in the brain, expressing neurosteroïdogenic cytochromes P450 and producing various neurosteroids. Cytochrome P450 epoxygenase enzymes, which catalyze the formation of vasoactive compounds are also present in astrocytes, contributing to the regulation of the cerebral blood flow. PERSPECTIVES AND CONCLUSION: This review underlines the crucial roles of astroglial cytochromes P450 in brain functions. Identification of the molecular mechanisms involved in the regulation of these enzymes could open therapeutic perspectives and improve our understanding in neuroprotection.
Authors: Bruno Penas Seara Pitanga; Ravena P Nascimento; Victor Diógenes A Silva; Silvia L Costa Journal: Front Pharmacol Date: 2012-08-03 Impact factor: 5.810