Neuroglobin-enriched secretome provides neuroprotection against hydrogen peroxide and mitochondrial toxin-induced cellular stress
Authors:Giovanna Bastari1,a, Virginia Solar Fernandez1,2,a, Maurizio Muzzi3,4, Sandra Moreno3,5, Maria Marino1,5 and Marco Fiocchetti1,5
1 Department of Science, Section Biomedical Sciences and Technology, University Roma Tre, V.le G. Marconi, 446, 00146, Rome, Italy. 2 Present address: Instituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSIC, Arturo Duperier, 4, 28029 Madrid, Spain; Department of Biochemistry, School of Medicine, Universidad Autonóma de Madrid, 28029 Madrid, Spain. 3 Department of Science, Section Molecular, Cellular, Environmental and Evolutionary Biology, LIME, University Roma Tre, V.le G. Marconi, 446, 00146, Rome, Italy. 4 Department of Bioscience and Territory, University of Molise, Contrada Fonte Lappone, 86090, Pesche, Italy. 5 IRCCS Fondazione Santa Lucia, via del Fosso di Fiorano, 64, 00179, Rome, Italy.
a Equal contribution as a first author.
Keywords:
neuroglobin, secretome, neuronal stress, neurodegeneration, mitochondria.
Abbreviations:
3-NP - 3-nitropropionic acid,
CM - conditioned medium,
EV - extracellular vesicle,
NGB - neuroglobin,
sEV - small EV,
WT - wild type.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Giovanna Bastari, Virginia Solar Fernandez, Maurizio Muzzi, Sandra Moreno, Maria Marino, Marco Fiocchetti (2024). Neuroglobin- enriched secretome provides neuroprotection against hydrogen peroxide and mitochondrial toxin-induced cellular stress. Cell Stress 8: 99-111. doi: 10.15698/cst2024.11.300
© 2024 Bastari et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Aberrant response to physiological cell stress is part of the mechanisms underlying the development of diverse human diseases, including neuropatholo- gies. Neuroglobin (NGB), an intracellular monomeric globin, has gained attention for its role in endogenous stress response pathways in neuroprotection. To date, evidence supports the concept of NGB as an inducible protein, triggered by phys- iological and pathological stimuli via transcriptional and/or post-transcriptional mechanisms, offering cell-autonomous neuroprotective functions under various cellular stresses. Notably, recent evidence suggests the extracellular occurrence of NGB. We aimed to explore whether NGB redistribution in the cell microenvi- ronment may serve in transmitting resilience capability in a model with neuronal characteristics. Results obtained in SH-SY5Y demonstrated that intracellular NGB upregulation is associated with the promotion of the extracellular release of the globin. Additionally, cell secretome from NGB-overexpressing cells, characterized by globin accumulation, exhibits protective effects against oxidative stress and mitochondrial toxicity, as evidenced by reduced apoptosis and preserved mito- chondrial structure. These findings shed light on the potential significance of extracellular NGB as part of a common cell response to physiological and stress conditions and as a factor promoting cell resilience. Furthermore, the potential for neuroprotection of extracellular NGB paves the way for future therapeutic opportunities.