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CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia
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| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | The Journal of Neuroscience, 28, 2008, 45, S. 11488-11499 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
|
| Schlagwörter: |
| author_facet |
Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele |
|---|---|
| author |
Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele |
| spellingShingle |
Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele The Journal of Neuroscience CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia General Neuroscience |
| author_sort |
milton, rosemary h. |
| spelling |
Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2431-08.2008 <jats:p>The Alzheimer's disease (AD) brain is characterized by plaques containing β-amyloid (Aβ) protein surrounded by astrocytes and reactive microglia. Activation of microglia by Aβ initiates production of reactive oxygen species (ROS) by the plasmalemmal NADPH oxidase; the resultant oxidative stress is thought to contribute to neurodegeneration in AD. We have previously shown that Aβ upregulates a chloride current mediated by the chloride intracellular channel 1 (CLIC1) protein in microglia. We now demonstrate that Aβ promotes the acute translocation of CLIC1 from the cytosol to the plasma membrane of microglia, where it mediates a chloride conductance. Both the Aβ induced Cl<jats:sup>−</jats:sup>conductance and ROS generation were prevented by pharmacological inhibition of CLIC1, by replacement of chloride with impermeant anions, by an anti-CLIC1 antibody and by suppression of CLIC1 expression using siRNA. Thus, the CLIC1-mediated Cl<jats:sup>−</jats:sup>conductance is required for Aβ-induced generation of neurotoxic ROS by microglia. Remarkably, CLIC1 activation is itself dependent on oxidation by ROS derived from the activated NADPH oxidase. We therefore propose that CLIC1 translocation from the cytosol to the plasma membrane, in response to redox modulation by NADPH oxidase-derived ROS, provides a feedforward mechanism that facilitates sustained microglial ROS generation by the NAPDH oxidase.</jats:p> CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia The Journal of Neuroscience |
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10.1523/jneurosci.2431-08.2008 |
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Society for Neuroscience, 2008 |
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Society for Neuroscience, 2008 |
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The Journal of Neuroscience |
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49 |
| title |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_unstemmed |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_full |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_fullStr |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_full_unstemmed |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_short |
CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_sort |
clic1 function is required for β-amyloid-induced generation of reactive oxygen species by microglia |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.2431-08.2008 |
| publishDate |
2008 |
| physical |
11488-11499 |
| description |
<jats:p>The Alzheimer's disease (AD) brain is characterized by plaques containing β-amyloid (Aβ) protein surrounded by astrocytes and reactive microglia. Activation of microglia by Aβ initiates production of reactive oxygen species (ROS) by the plasmalemmal NADPH oxidase; the resultant oxidative stress is thought to contribute to neurodegeneration in AD. We have previously shown that Aβ upregulates a chloride current mediated by the chloride intracellular channel 1 (CLIC1) protein in microglia. We now demonstrate that Aβ promotes the acute translocation of CLIC1 from the cytosol to the plasma membrane of microglia, where it mediates a chloride conductance. Both the Aβ induced Cl<jats:sup>−</jats:sup>conductance and ROS generation were prevented by pharmacological inhibition of CLIC1, by replacement of chloride with impermeant anions, by an anti-CLIC1 antibody and by suppression of CLIC1 expression using siRNA. Thus, the CLIC1-mediated Cl<jats:sup>−</jats:sup>conductance is required for Aβ-induced generation of neurotoxic ROS by microglia. Remarkably, CLIC1 activation is itself dependent on oxidation by ROS derived from the activated NADPH oxidase. We therefore propose that CLIC1 translocation from the cytosol to the plasma membrane, in response to redox modulation by NADPH oxidase-derived ROS, provides a feedforward mechanism that facilitates sustained microglial ROS generation by the NAPDH oxidase.</jats:p> |
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| author | Milton, Rosemary H., Abeti, Rosella, Averaimo, Stefania, DeBiasi, Silvia, Vitellaro, Laura, Jiang, Lele, Curmi, Paul M. G., Breit, Samuel N., Duchen, Michael R., Mazzanti, Michele |
| author_facet | Milton, Rosemary H., Abeti, Rosella, Averaimo, Stefania, DeBiasi, Silvia, Vitellaro, Laura, Jiang, Lele, Curmi, Paul M. G., Breit, Samuel N., Duchen, Michael R., Mazzanti, Michele, Milton, Rosemary H., Abeti, Rosella, Averaimo, Stefania, DeBiasi, Silvia, Vitellaro, Laura, Jiang, Lele, Curmi, Paul M. G., Breit, Samuel N., Duchen, Michael R., Mazzanti, Michele |
| author_sort | milton, rosemary h. |
| container_issue | 45 |
| container_start_page | 11488 |
| container_title | The Journal of Neuroscience |
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| description | <jats:p>The Alzheimer's disease (AD) brain is characterized by plaques containing β-amyloid (Aβ) protein surrounded by astrocytes and reactive microglia. Activation of microglia by Aβ initiates production of reactive oxygen species (ROS) by the plasmalemmal NADPH oxidase; the resultant oxidative stress is thought to contribute to neurodegeneration in AD. We have previously shown that Aβ upregulates a chloride current mediated by the chloride intracellular channel 1 (CLIC1) protein in microglia. We now demonstrate that Aβ promotes the acute translocation of CLIC1 from the cytosol to the plasma membrane of microglia, where it mediates a chloride conductance. Both the Aβ induced Cl<jats:sup>−</jats:sup>conductance and ROS generation were prevented by pharmacological inhibition of CLIC1, by replacement of chloride with impermeant anions, by an anti-CLIC1 antibody and by suppression of CLIC1 expression using siRNA. Thus, the CLIC1-mediated Cl<jats:sup>−</jats:sup>conductance is required for Aβ-induced generation of neurotoxic ROS by microglia. Remarkably, CLIC1 activation is itself dependent on oxidation by ROS derived from the activated NADPH oxidase. We therefore propose that CLIC1 translocation from the cytosol to the plasma membrane, in response to redox modulation by NADPH oxidase-derived ROS, provides a feedforward mechanism that facilitates sustained microglial ROS generation by the NAPDH oxidase.</jats:p> |
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| imprint_str_mv | Society for Neuroscience, 2008 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| physical | 11488-11499 |
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| spelling | Milton, Rosemary H. Abeti, Rosella Averaimo, Stefania DeBiasi, Silvia Vitellaro, Laura Jiang, Lele Curmi, Paul M. G. Breit, Samuel N. Duchen, Michael R. Mazzanti, Michele 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.2431-08.2008 <jats:p>The Alzheimer's disease (AD) brain is characterized by plaques containing β-amyloid (Aβ) protein surrounded by astrocytes and reactive microglia. Activation of microglia by Aβ initiates production of reactive oxygen species (ROS) by the plasmalemmal NADPH oxidase; the resultant oxidative stress is thought to contribute to neurodegeneration in AD. We have previously shown that Aβ upregulates a chloride current mediated by the chloride intracellular channel 1 (CLIC1) protein in microglia. We now demonstrate that Aβ promotes the acute translocation of CLIC1 from the cytosol to the plasma membrane of microglia, where it mediates a chloride conductance. Both the Aβ induced Cl<jats:sup>−</jats:sup>conductance and ROS generation were prevented by pharmacological inhibition of CLIC1, by replacement of chloride with impermeant anions, by an anti-CLIC1 antibody and by suppression of CLIC1 expression using siRNA. Thus, the CLIC1-mediated Cl<jats:sup>−</jats:sup>conductance is required for Aβ-induced generation of neurotoxic ROS by microglia. Remarkably, CLIC1 activation is itself dependent on oxidation by ROS derived from the activated NADPH oxidase. We therefore propose that CLIC1 translocation from the cytosol to the plasma membrane, in response to redox modulation by NADPH oxidase-derived ROS, provides a feedforward mechanism that facilitates sustained microglial ROS generation by the NAPDH oxidase.</jats:p> CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia The Journal of Neuroscience |
| spellingShingle | Milton, Rosemary H., Abeti, Rosella, Averaimo, Stefania, DeBiasi, Silvia, Vitellaro, Laura, Jiang, Lele, Curmi, Paul M. G., Breit, Samuel N., Duchen, Michael R., Mazzanti, Michele, The Journal of Neuroscience, CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia, General Neuroscience |
| title | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_full | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_fullStr | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_full_unstemmed | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_short | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| title_sort | clic1 function is required for β-amyloid-induced generation of reactive oxygen species by microglia |
| title_unstemmed | CLIC1 Function Is Required for β-Amyloid-Induced Generation of Reactive Oxygen Species by Microglia |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.2431-08.2008 |