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Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan May 2008

Atf4 Is An Oxidative Stress–Inducible, Prodeath Transcription Factor In Neurons In Vitro And In Vivo, Philipp Lange, Juan Chavez, John T. Pinto, Giovanni Coppola, Chiao-Wang Sun, Tim Townes, Rajiv Ratan

NYMC Faculty Publications

Oxidative stress is pathogenic in neurological diseases, including stroke. The identity of oxidative stress-inducible transcription factors and their role in propagating the death cascade are not well known. In an in vitro model of oxidative stress, the expression of the bZip transcription factor activating transcription factor 4 (ATF4) was induced by glutathione depletion and localized to the promoter of a putative death gene in neurons. Germline deletion of ATF4 resulted in a profound reduction in oxidative stress-induced gene expression and resistance to oxidative death. In neurons, ATF4 modulates an early, upstream event in the death pathway, as resistance to oxidative …


Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy Dec 2000

Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy

NYMC Faculty Publications

Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …