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Over 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. © IUBMB IUBMB Life, 62(12): 878-885, 2010. [ABSTRACT FROM AUTHOR]

Neuroglobin has been identified to protect brain neurons from apoptotic stress. Hydrogen sulphide has a role in the brain as a neuromodulator, involving NMDA receptor activation. Here we report on studies of the in vitro interaction of ferric neuroglobin with hydrogen sulphide. Hydrogen sulphide binds very tightly to the heme group of neuroglobin in a biphasic reaction. The faster of the two reaction processes is concentration dependent whilst the slower process is not. The rate of hydrogen sulphide binding is pH sensitive and as the pH is reduced over the physiological range the rate of reaction increases by a factor of ∼10. This change in reactivity appears to reflect the ionisation of the heme distal His ligand rather than a preference for the binding of H2S. We discuss the potential role of neuroglobin in the modulation of hydrogen sulphide sensitivity of neurons in the brain. © 2008 IUBMB IUBMB Life, 60(2): 135–138, 2008 [ABSTRACT FROM AUTHOR]