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• W3136303711 startingPage "107509" @default.
• W3136303711 abstract "B cells play a major role in regulating disease incidence through various factors, including spleen tyrosine kinase (Syk), which transmits signals to all hematopoietic lineage cells. Hypoxia-inducible factor (HIF)-1α accumulates under hypoxic conditions, which is also oxidative stress to induce nuclear factor (erythroid-derived 2)-like 2 (Nrf2) responsible for gene expression of antioxidant enzymes. In the present study, we investigated whether B cells are regulated by crosstalk of HIF-1α and Nrf2 via reactive oxygen species (ROS)-mediated Syk activation. When B cells were incubated under hypoxic conditions, Syk phosphorylation, HIF-1α, and Nrf2 levels were increased. Hypoxia-inducible results were consistent with CoCl2 treatment, which mimics hypoxic conditions. Cell viability was reduced by the Syk inhibitor BAY 61-3606. Increased Nrf2 levels due to hypoxia or CoCl2 were inhibited by treatment with a HIF inhibitor. Hypoxia- or CoCl2-induced ROS increased HIF-1α and Nrf2 levels, which were attenuated by treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. HIF-1α levels were reduced in doxycycline-treated shNrf2 cells. Clobetasol propionate, a Nrf2 inhibitor, also inhibited HIF-1α levels induced by hypoxia or CoCl2. ROS-mediated Syk phosphorylation at tyrosine 525/526 was confirmed by treatment with H2O2, hypoxia, and CoCl2, and attenuated with NAC treatment. Inhibition of Syk phosphorylation by BAY 61-3606 is consistent with a decrease in protein HIF-1α and Nrf2 levels. Taken together, HIF-1α levels might control Nrf2 levels and vice versa, and could be associated with Syk phosphorylation in B cells. The results indicate that B cells could be regulated by crosstalk of HIF-1α and Nrf2 through ROS-mediated Syk activation." @default.
• W3136303711 created "2021-03-29" @default.
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• W3136303711 date "2021-06-01" @default.
• W3136303711 modified "2023-10-13" @default.
• W3136303711 title "Spleen tyrosine kinase regulates crosstalk of hypoxia-inducible factor-1α and nuclear factor (erythroid-derived2)-like 2 for B cell survival" @default.
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• W3136303711 doi "https://doi.org/10.1016/j.intimp.2021.107509" @default.
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