HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-100784v1 22/6/1737    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Khan, A. A. Articles by Greenberg, D. A. PubMed PubMed Citation Articles by Khan, A. A. Articles by Greenberg, D. A.

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

¹Correspondence: The Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA. E-mail: akhan{at}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