Differential association of 4E-BP2-interacting proteins is related to selective delayed neuronal death after ischemia

Impacto

Downloads

Downloads per month over past year

Martínez Alonso, Emma and Guerra Pérez, Natalia and Escobar Peso, Alejandro and Regidor, Ignacio and Masjuan, Jaime and Alcázar González, Alberto (2021) Differential association of 4E-BP2-interacting proteins is related to selective delayed neuronal death after ischemia. International Journal of Molecular Sciences, 22 (19). pp. 1-22. ISSN 1422-0067, Electronic: 1422-0067

[thumbnail of Martínez-Alonso, E. et al. 2021. Differential association of 4e-bp2-interacting proteins....pdf]
Preview
PDF
Creative Commons Attribution.

2MB

Official URL: https://doi.org/10.3390/ijms221910327




Abstract

Cerebral ischemia induces an inhibition of protein synthesis and causes cell death and neuronal deficits. These deleterious effects do not occur in resilient areas of the brain, where protein synthesis is restored. In cellular stress conditions, as brain ischemia, translational repressors named eukaryotic initiation factor (eIF) 4E-binding proteins (4E-BPs) specifically bind to eIF4E and are critical in the translational control. We previously described that 4E-BP2 protein, highly expressed in brain, can be a molecular target for the control of cell death or survival in the reperfusion after ischemia in an animal model of transient cerebral ischemia. Since these previous studies showed that phosphorylation would not be the regulation that controls the binding of 4E-BP2 to eIF4E under ischemic stress, we decided to investigate the differential detection of 4E-BP2-interacting proteins in two brain regions with different vulnerability to ischemia-reperfusion (IR) in this animal model, to discover new potential 4E-BP2 modulators and biomarkers of cerebral ischemia. For this purpose, 4E-BP2 immunoprecipitates from the resistant cortical region and the vulnerable hippocampal cornu ammonis 1 (CA1) region were analyzed by two-dimensional (2-D) fluorescence difference in gel electrophoresis (DIGE), and after a biological variation analysis, 4E-BP2-interacting proteins were identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Interestingly, among the 4E-BP2-interacting proteins identified, heat shock 70 kDa protein-8 (HSC70), dihydropyrimidinase-related protein-2 (DRP2), enolase-1, ubiquitin carboxyl-terminal hydrolase isozyme-L1 (UCHL1), adenylate kinase isoenzyme-1 (ADK1), nucleoside diphosphate kinase-A (NDKA), and Rho GDP-dissociation inhibitor-1 (Rho-GDI), were of notable interest, showing significant differences in their association with 4E-BP2 between resistant and vulnerable regions to ischemic stress. Our data contributes to the first characterization of the 4E-BP2 interactome, increasing the knowledge in the molecular basis of the protection and vulnerability of the ischemic regions and opens the way to detect new biomarkers and therapeutic targets for diagnosis and treatment of cerebral ischemia.


Item Type:Article
Uncontrolled Keywords:Cerebral ischemia; eIF4E-binding protein; eIF4E; Protein synthesis regulation; Protein complexes; Neuronal death; Vulnerable regions; Neuroprotection; Proteomics
Subjects:Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:72170
Deposited On:10 May 2022 07:42
Last Modified:10 May 2022 08:21

Origin of downloads

Repository Staff Only: item control page