Fig 2: Sunitinib induces excessive ROS which activates MAPKs, thereby inducing apoptosis and autophagy in L02 cells. (A) L02 cells were exposed with Sunitinib at 15 μM for 6, 9, 12, 24 h. ROS levels were analyzed using a ROS assay kit. Green fluorescence was observed on fluorescence microscopy (scale bars = 50 μm). (B) Quantification of ROS intensities. (C) The viability of hepatocytes was analyzed by MTT after L02 cells were incubated with 5 μM, 10 μM, and 15 μM Sunitinib for 48 h in the presence or absence of 10 mM NAC pretreatment for 6 h (n = 6). (D) ALT, AST, and LDH levels in the supernatant after L02 cells were incubated with 15 μM Sunitinib for 48 h in the presence or absence of 10 mM NAC pretreatment for 6 h (n = 3). (E,F) Protein expression of p-JNK/JNK, p-ERK/ERK, and p-P38/P38 after L02 cells were incubated with 10 μM Sunitinib for 12 h in the presence or absence of 10 mM NAC pretreatment for 6 h (n = 3). (G,H) LC3B levels in L02 cells after Sunitinib (15 μM) for 48 h in the presence or absence of 10 mM NAC pretreatment for 6 h (n = 3). *p < 0.05, **p < 0.01, and ***p < 0.001 vs. Control group. # p < 0.05, ## p < 0.01 and ### p < 0.001 vs. Sunitinib group.

Fig 3: The graphic overview of this study. The phosphate groups transported from activated MAPK/ERK pathway and LRRK2 to HDAC3 causes the repression of H3K9ac and results in a large number of gene expression silencing in trigeminal ganglion induced by compressive stress.