Book of abstracts - British Neuroscience Association

11.08
Chloride intracellular channel 1 (clic1) plays a central role in
regulating free radical generation by microglia in response to
Beta-amyloid
Milton R H, Abeti R, Duchen M R, Mazzanti M
Deaprtment of Phsyiology, University College London, , Gower Street,
WC1E 6BT, , Dipartimento di Scienze Biomolecolari e Biotecnologie,
Universita` degli Studi di Milano, Via Celoria 26, 20133 Milano, Italy,
β-Amyloid (Aβ) peptides accumulate in the brain in Alzheimer’s
Disease (AD) and are implicated in its pathogenesis. Microglia, the
immune cells of the CNS, are activated by Aβ and in response,
produce reactive oxygen species (ROS) through activation of the
plasmalemmal NADPH oxidase. Generation of ROS by microglia is
thought to contribute to the cell death seen in AD. We have previously
shown that Aβ activates a chloride current mediated by the protein
CLIC1 (Novarino et al, 2004). We now show that Aβ-induced
microglial ROS production is contingent upon the channel activity of
CLIC1. Rates of ROS generation were measured using hydroethidium
fluorescence from BV2 and primary microglial cells. Suppression of
CLIC1 protein expression using siRNA, inhibition of the CLIC1 chloride
current using IAA-94 or using an antibody to the channel protein, and
replacement of extracellular Cl- with impermeant anions, all
significantly reduced the ROS response to Aβ (p