Fig. 4

The ATF4/CHOP pathway is a downstream target of SRPK1 inhibition. A YT cells were transfected with SRPK1 siRNA or treated with SPHINX31 (12.5 μM) or SRPIN340 (12.5 μM) for 24 h. Gene Ontology (GO) enrichment analysis showed that multiple pathways were affected by SRPK1 downregulation. (①: intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ②: negative regulation of oxidative stress-induced neuron death; ③: positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress). B Western blotting showed that CHOP and AFT4 were upregulated by SRPK1 silencing and inhibition. C Silencing ATF4 by siRNA transfection decreased the expression of ATF4 in YT cells. D Annexin V/7-AAD double staining showed the effect of ATF4 knockdown by siRNA on SPHINX31-induced apoptosis in YT cells.