Glycogen synthase kinase-3 beta inhibitor SB216763 promotes DNA repair in ischemic retinal neurons

摘要

Glycogen synthase kinase-3 beta (GSK-3 beta) has been shown to attenuate DNA damage in nerve cells, thereby enhancing neuronal survival under pathological conditions; however, the underlying mechanism remains unclear. An in vitro serum-starvation retinal neuron model and in vivo ischemia/reperfusion retina injury rat model were established and treated with SB216763, a GSK-3 beta inhibitor. SB21673 decreased the formation of gamma-H2A histone family member X foci and enhanced the viability of ischemic retinal neurons. In addition, SB216763 upregulated expression of phosphorylated-CREB1, a ligase IV transcription factor, and significantly increased the transcriptional activity of ligase IV in ischemic retinal neurons. These results were confirmed in rat retinas following ischemia/reperfusion injury. Furthermore, we found that unlike lithium chlorine (a well-known direct inhibitor of GSK-3 beta), SB216763 inhibited GSK-3 beta activity by suppressing its phosphorylation. Taken together, our results suggest that GSK-3 beta inhibition enhances repair of DNA double-strand breaks by upregulating ligase IV expression in ischemic retinal neurons.

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