Regulation of hypoxic neuronal death signaling by neuroglobin Adil A. Khan * ,1 , Xiao Ou Mao * , Surita Banwait * , Celine M. DerMardirossian † , Gary M. Bokoch † , Kunlin Jin * and David A. Greenberg * * The Buck Institute for Age Research, Novato, California, USA; and † Department of Cell Biology, The Scripps Research Institute, La Jolla, California, USA 1 Correspondence: The Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA. E-mail: akhan@buckinstitute.org The signal transduction pathways involved in neuronal death are not well understood. Neuroglobin (Ngb), a recently discovered vertebrate globin expressed predominantly in the brain, shows increased expression in neurons in response to oxygen deprivation and protects neurons from ischemic and hypoxic death. The mechanism of this neuroprotection is unclear. We examined the surface distribution of raft membrane microdomains in cortical neuron cultures during hypoxia using the raft marker cholera toxin B (CTx-B) subunit. Mechanistically, we demonstrate that hypoxia induces rapid polarization of somal membranes and aggregation of microdomains with the subjacent mitochondrial network. This signaling complex is formed well before neurons commit to die, consistent with an early role in death signal transduction. Neurons from Ngb-overexpressing transgenic (Ngb-Tg) mice do not undergo microdomain polarization or mitochondrial aggregation in response to, and are resistant to death from hypoxia. We link the protective actions of Ngb to inhibition of Pak1 kinase activity and Rac1-GDP-dissociation inhibitor disassociation, and inhibition of actin assembly and death-signaling module polarization.—Khan, A. A., Mao, X. O., Banwait, S., DerMardirossian, C. M., Bokoch, G. M., Jin, K., Greenberg, D. A. Regulation of hypoxic neuronal death signaling by neuroglobin. Key Words: soma • polarity • DISC • death-inducing signaling complex
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Regulation of hypoxic neuronal death signaling by neuroglobin
Khan, Adil A.; Mao, Xiao Ou; Banwait, Surita; DerMardirossian, Celine M.; Bokoch, Gary M.; Jin, Kunlin; Greenberg, David A.
Follow The FASEB Journal
, Volume 22 (6): 1737
Fed of American Socs for Experimental Biology – Jun 1, 2008
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