Phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α) alleviates benzo[a]pyrene-7,8-diol-9,10-epoxide induced cell cycle arrest and apoptosis in human cells

Experimental Evidence Shows Salubrinal, an eIF2α Dephosphorylation Inhibitor, Reduces Xenotoxicant-Induced Cellular Damage

“…However, the mechanisms underlying the cytoprotection conferred by salubrinal are extremely complex, and might differ depending on the nature and the severity of the insult, as well as the cell type being investigated. The enhancement or prolongation of xenotoxicant-induced eIF2α phosphorylation is observed in a number of experiments [ 12 , 25 , 26 , 27 , 28 , 29 ]; this concurs with the ability of salubrinal to prevent eIF2α dephosphorylation [ 9 ]. The resultant inhibition of global protein synthesis alleviates the workload on the ER, and subsequently reduces energy consumption, leading to cell survival ( Figure 2 ).…”

“…The BPDE-induced DNA damage blocks cell cycle progression and induces apoptosis. Pretreatment of human amniotic epithelial cells with 20 µM salubrinal for 30 min prolongs BPDE (0.5 and 1 µM)-induced eIF2α phosphorylation until 48 h after exposure [ 27 ]. Salubrinal attenuates cell cycle arrest after 24 or 30 h, and DNA fragmentation and nuclear condensation after 48 h exposure to 0.5 µM BPDE.…”

Time- and Oil-Dependent Transcriptomic and Physiological Responses to Deepwater Horizon Oil in Mahi-Mahi (Coryphaena hippurus) Embryos and Larvae

“…37 EIF2 signaling was identified in the top 3 most significantly affected canonical pathways from the differential exon usage (DEU) genes in 96 hpf zebrafish larvae exposed to BaP. 38 Wang et al 39 demonstrated that a benzo[a]pyrene metabolite BPDE induced severe cell cycle arrest, apoptosis and decreased cell viability in human amnion epithelial cells, and EIF2 α phosphorylation produced a pro-survival and antiapoptotic effect to alleviate the cellular damage. In the present study, the decreased activity in the EIF2 signaling pathway at 24 hpf followed by increased activity at 96 hpf by both source and slick oil exposure may indicate the 24 hpf stage is more susceptible to embryo lethality since the adaptive response was diminished.…”

Attenuation of the unfolded protein response and endoplasmic reticulum stress after mechanical unloading in dilated cardiomyopathy

“…After mechanical unloading, we found remission of the UPR markers studied together with a decrease in apoptosis rate: BiP is a master switch that activates the different UPR branches, whereas eIF2␣ activates apoptosis, and XBP1s transcriptionally induces ER stress genes. Although cardioprotective actions of activated eIF2␣ and XBP1 have also been reported (22,35), our results indicate that UPR normalization by LVAD may be preventing ongoing apoptosis and cell loss. This deactivation of the UPR is probably a direct consequence of an improvement in Ca 2ϩ cycling in cardiomyocytes and the ER, as suggested by correlation between SERCA2a and XBP1s/XBP1 improvement and supported by the effect of SERCA2a inactivation in AC16 cells.…”