Differential Association of 4E-BP2-Interacting Proteins Is Related to Selective Delayed Neuronal Death after Ischemia

Autor: Alejandro Escobar-Peso, Emma Martínez-Alonso, Alberto Alcázar, Natalia Guerra-Pérez, Jaime Masjuan, Ignacio Regidor
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
protein synthesis regulation
Proteomics
Interactome
cerebral ischemia
Brain Ischemia
Brain ischemia
Ubiquitin
Eukaryotic initiation factor
Eukaryotic Initiation Factors
Phosphorylation
Biology (General)
Spectroscopy
Cerebral Cortex
Neurons
biology
Cell Death
Chemistry
General Medicine
neuronal death
Computer Science Applications
Cell biology
Reperfusion Injury
neuroprotection
Protein Binding
Bioquímica
Programmed cell death
QH301-705.5
Neurociencias
Ischemia
Neuroprotection
Catalysis
Article
Inorganic Chemistry
proteomics
eIF4E-binding protein
medicine
Animals
Physical and Theoretical Chemistry
Rats
Wistar
Molecular Biology
CA1 Region
Hippocampal
QD1-999
protein complexes
Organic Chemistry
medicine.disease
Phosphoproteins
Rats
vulnerable regions
Protein Biosynthesis
eIF4E
biology.protein
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 10327, p 10327 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 19
E-Prints Complutense. Archivo Institucional de la UCM
instname
ISSN: 1661-6596
1422-0067
Popis: 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.
Databáze: OpenAIRE
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