A role for human neuroglobin in apoptosis

Abstract

SummaryOver the past decade, following the discovery of the human heme protein neuroglobin, many studies have searched for evidence for this protein's mechanism of action. Much data has accrued showing that high levels of neuroglobin will protect cells from apoptotic cell death, following a wide range of challenges. Various explanations of its actions, based on measured reactivity with oxygen, nitric oxide, or free radicals, have been proposed, but none have, as yet, been substantiated in vivo. Following preliminary experiments, it was previously hypothesised that ''the central role of neuroglobin in highly metabolically active cells and retinal and brain neurons is to reset the trigger level of mitochondrial cytochrome c release necessary to commit the cells to apoptosis'' (I.U.M.B.M. Life (2008) 60, 398). In this article, we review the evidence, which has accumulated to support this hypothesised mechanism of action of neuroglobin and integrate this data, with other reported intracellular functions of neuroglobin, to suggest a plausible central role for neuroglobin in the control of apoptosis. IUBMBIUBMB Life, 62(12): 878-885, 2010

Neurorestorative Targets of Dietary Long-Chain Omega-3 Fatty Acids in Neurological Injury

“…The globin fold also enables the tissue hemoglobin to serve as either a facilitator of oxygen transport within a cell, a scavenger of nitric oxide, and/or an enzyme with peroxidase activity. Hemoproteins such as cytoglobin (CYGB) neuroglobin (Ngb) have been implicated in mediating neurorestorative responses in models of hypoxia-ischemia and spinal cord trauma [58–60]. Although LC-O3PUFAs may also prevent the degradation of these key proteins, the effects of dietary LC-O3PUFAs on this important family needs to be clarified and further characterized.…”

Neuroglobin, a Factor Playing for Nerve Cell Survival

“…As pointed out by Brittain et al and Yu et al [12,58], in many of the above mentioned studies, where NGB exhibited a significant effect on nerve cell survival, parameters linked to mitochondrial functions were significantly affected by NGB expression. They include ATP production [45] and reactive oxygen species (ROS) generation [34,39,48].…”

“…These findings, together with evidence showing that NGB expression is basically confined to metabolically active, oxygen-consuming cell types (see Section 2.1), led to the hypothesis that mechanisms triggered by NGB could induce neuroprotection by modulating mitochondria function and regulation (see [12,58] for reviews). The exact processes, however, are still under careful investigation.…”

Conformational Dynamics Associated with Ligand Binding to Vertebrate Hexa-coordinate Hemoglobins

“…An increased level of Ngb expression also promotes neuron survival after ischemic insults (Sun et al, 2001;Sun et al, 2003). The molecular basis of the neuroprotective function of Ngb remains unclear, but several plausible mechanisms have been proposed, including oxygen storage (Dewilde et al, 2001;Sun et al, 2001), oxygen/redox sensing (Wakasugi et al, 2003), decomposition of reactive oxygen species (Herold et al, 2004;Van Doorslaer et al, 2003), and inhibition of apoptosis (Brittain et al, 2010a;Fago et al, 2006). In addition, Wakasugi et al (2003) reported that ferric Ngb binds to the GDP-bound form of the α-subunit of the heterotrimeric G protein acting as a guanine nucleotide dissociation inhibitor and the interactions between hNgb and the G protein may promote cell survival (Wakasugi et al, 2011).…”

“…In addition, Wakasugi et al (2003) reported that ferric Ngb binds to the GDP-bound form of the α-subunit of the heterotrimeric G protein acting as a guanine nucleotide dissociation inhibitor and the interactions between hNgb and the G protein may promote cell survival (Wakasugi et al, 2011). Alternatively, Brittain et al (2010a;2010b) showed that in vivo Ngb inhibits apoptosis through the binding to cytochrome c and preventing pro-caspase 9 activation.…”