Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model
AbstractNeuroglobin is a heme protein of which increased levels provide neuroprotection against amyloid proteinopathy and hemorrhagic damage. These cellular stressors involve the promotion of ferroptosis—an iron-dependent, lipid peroxide-accreting form of cell death. Hence, we questioned whether neuroglobin could oppose ferroptosis initiation. We detected human neuroglobin (hNgb)-EGFP-expressing SH-SY5Y cells to be significantly more resistant to ferroptosis induction, identifying 0.68-fold less cell death. To elucidate the underlying pathways, this study investigated hNgb-protein interactions with a Co-IP-MS/MS approach both under a physiological and a ferroptotic condition. hNgb binds to proteins of the cellular iron metabolism (e.g., RPL15 and PCBP3) in an unstressed condition and shows an elevated binding ratio towards cell death-linked proteins, such as HNRNPA3, FAM120A, and ABRAXAS2, under ferroptotic stress. Our data also reveal a constitutive interaction between hNgb and the longevity-associated heterodimer XRCC5/XRCC6. Disentangling the involvement of hNgb and its binding partners in cellular processes, using Ingenuity Pathway Analysis, resulted in the integration of hNgb in the ubiquitination pathway, mTOR signaling, 14-3-3-mediated signaling, and the glycolysis cascade. We also detected a previously unknown strong link with motor neuropathies. Hence, this study contributes to the elucidation of neuroglobin’s involvement in cellular mechanisms that provide neuroprotection and the upkeep of homeostasis. View Full-Text
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Van Acker, Z.P.; Van Raemdonck, G.A.; Logie, E.; Van Acker, S.I.; Baggerman, G.; Vanden Berghe, W.; Ponsaerts, P.; Dewilde, S. Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model. Cells 2019, 8, 873.
Van Acker ZP, Van Raemdonck GA, Logie E, Van Acker SI, Baggerman G, Vanden Berghe W, Ponsaerts P, Dewilde S. Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model. Cells. 2019; 8(8):873.Chicago/Turabian Style
Van Acker, Zoë P.; Van Raemdonck, Geert A.; Logie, Emilie; Van Acker, Sara I.; Baggerman, Geert; Vanden Berghe, Wim; Ponsaerts, Peter; Dewilde, Sylvia. 2019. "Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model." Cells 8, no. 8: 873.
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