title: Does a redox cycle provide a mechanism for setting the capacity of neuroglobin to protect cells from apoptosis?
abstract: We hypothesize that the various, previously reported, reactivities of neuroglobin with redox partners and oxygen provide for the establishment of a redox cycle within cells, such as neurons and retinal rod cells. Using native cell lysates, from cultured human cells of neuronal origin, we have estimated the rate of reduction of the oxidized form of neuroglobin in vivo. Furthermore we provide evidence that the cytosol of these cells contains factors (presumably enzymes) capable of employing either glutathione or NADH as re-reductants of ferric neuroglobin. Taken in conjunction with previous rate data, for the various redox reactions of neuroglobin, this information allows us to set up a computer model to estimate the steady state cellular level of the antiapoptotic ferrous form of neuroglobin. This model indicates that the steady state level of antiapoptotic neuroglobin is very sensitive to the cellular oxygen tension and moderately sensitive to the redox status of the cell. Further analysis indicates that such a system would be capable of significant modification, on the seconds time scale, following hypoxic transition, as is likely in stroke. We hypothesize that this mechanism might provide a moderately rapid mechanism for adjusting the antiapoptotic status of a cell, whilst the reaction of neuroglobin with mitochondrial cytochrome c provides a very rapid, but limited, capacity to intervene in the apoptotic pathway.
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand. T.Brittain@auckland.ac.nz
authors.forename: Thomas
authors.initials: T
authors.lastname: Brittain
authors.forename: Joanna
authors.initials: J
authors.lastname: Skommer
mesh_terms: D017209:Apoptosis; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D003198:Computer Simulation; D045304:Cytochromes c / Q000737:chemistry / Q000502:physiology; D005914:Globins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D000078787:Neuroglobin; D010084:Oxidation-Reduction
chemical_list: D002457:Cell Extracts; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D045304:Cytochromes c