The adaptor protein SH2B1β reduces hydrogen peroxide-induced cell death in PC12 cells and hippocampal neurons

Abstract

BackgroundSH2B1β is a signaling adaptor protein that has been shown to promote neuronal differentiation in PC12 cells and is necessary for the survival of sympathetic neurons. However, the mechanism by which SH2B1β may influence cell survival is not known.ResultsIn this study, we investigated the role of SH2B1β in oxidative stress-induced cell death. Our results suggest that overexpressing SH2B1β reduced H2O2-induced, caspase 3-dependent apoptosis in PC12 cells and hippocampal neurons. In response to H2O2, overexpressing SH2B1β enhanced PI3K (phosphatidylinositol 3-kinas)-AKT (protein kinase B) and MEK (MAPK/ERK kinase)-extracellular-signal regulated kinases 1 and 2 (ERK1/2) signaling pathways. We further demonstrated that SH2B1β was able to reduce H2O2-induced nuclear localization of FoxO1 and 3a transcription factors, which lie downstream of PI3K-AKT and MEK-ERK1/2 pathways. Moreover, overexpressing SH2B1β reduced the expression of Fas ligand (FasL), one of the target genes of FoxOs.ConclusionsOverexpressing the adaptor protein SH2B1β enhanced H2O2-induced PI3K-AKT and MEK-ERK1/2 signaling, reduced nucleus-localized FoxOs and the expression of a pro-apoptotic gene, FasL.

The C‐ETS2‐TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity

“…We then centrifuged and resuspended the cells in a neurobasal medium with 10% FBS and plated them onto polyethyleneimine-coated plates. After the cells were attached to the substrate, the medium was replaced with a neuronal culture medium (serum-free neurobasal medium with 2% B27, 0.5 mM glutamine, 100 U/mL penicillin, and 100 U/mL streptomycin) [ 16 , 17 ]. The medium was replaced every two days.…”

“…The SHY5Y cells and primary neurons were treated with H 2 O 2 at the indicated concentration for 4 h or were pretreated with bafilomycin A1 (50 μ M) [ 18 ], chloroquine (20 μ M) [ 19 ], and ammonium chloride (5 mM NH 4 Cl) for 1 h [ 20 ] and then exposed to H 2 O 2 [ 17 ].…”

The intensity of the processes of oxidative modification of proteins and the activity of enzymes of the antioxidant protection system of broiler chickens under the action of vitamins E and C

“…It is known that under conditions of oxidative stress and excessive generation of AEO, processes of uncontrolled protein modification is developing, that cause protein fragmentation, their denaturation, and also the formation of primary amino acid radicals, further engaging in secondary interaction with adjacent amino acid residues, and in general, it creates a rather complicated picture of the damaging action of AEO on protein macromolecules. All this leads to the loss of their biological activity by proteins and disruption of metabolic processes, in particular regenerative processes (Armstrong, 2002;Martyshuk et al, 2016;Lavryshyn et al, 2016;Gutyj et al, 2018;Lavryshyn & Gutyj, 2019).…”

SH2B1 increases the numbers of IRSp53-induced filopodia

“…Four SH2B1 splice variants, α, β, γ and δ, have been identified so far [26,27,36]. SH2B1 promotes neurite initiation, outgrowth and neuronal survival of PC12 cells, cortical and hippocampal neurons [31,35,37,38]. Besides general function as a signaling adaptor protein, SH2B1β also acts as a nuclear protein which shuttles between cytosol and nucleus to regulate expression of genes such as MMP3, MMP10, uPAR, Egr1 and Cdh2 [39][40][41].…”