Dataset Information


Connecting the Dots in the Neuroglobin-Protein Interaction Network of an Unstressed and Ferroptotic Cell Death Neuroblastoma Model.

ABSTRACT: Neuroglobin 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.


PROVIDER: S-EPMC6721670 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6449247 | BioStudies
1000-01-01 | S-EPMC5034113 | BioStudies
2019-01-01 | S-EPMC6602333 | BioStudies
2020-01-01 | S-EPMC7008777 | BioStudies
2020-01-01 | S-EPMC7172030 | BioStudies
2019-01-01 | S-EPMC6786318 | BioStudies
1000-01-01 | S-EPMC5666033 | BioStudies
2020-01-01 | S-EPMC7283515 | BioStudies
2018-01-01 | S-EPMC6262011 | BioStudies
2020-01-01 | S-EPMC7353921 | BioStudies