We then analyzed how DMS at low micromolar range scavenged ROS in PC12 cells. Considering the intrinsic catalytic function of MsrA in the oxidation of thiomethyl groups, we tested whether the antioxidation effect of DMS is dependent on MsrA. After treatment with lentiviral‐expressed specific short hairpin RNAs (shRNA) against MsrA (Fig. S6), the expression level of MsrA decreased to 22 ± 6% (n = 6, P < 0.01 vs. control). As shown in Fig. 5A,B, DMS decreased the AA‐induced superoxide production in PC12 cells from 178 ± 8% of control group to 129 ± 8% (P < 0.01). However, in MsrA shRNA group, the effect of DMS (10 μm) on AA‐induced superoxide production was abolished (Fig. 5C,D, 241 ± 13% in DMS group vs. 212 ± 14% in AA group of MsrA shRNA), suggesting that MsrA‐catalytic oxidation of thiomethyl group is involved in DMS‐mediated antioxidation. After MsrA knockdown by shRNA, the protective effect of DMS (5 μm) on cell viability against H2O2 was also abolished. With control shRNA, the DMS increased the cell viability of PC12 cells from 68 ± 2% in H2O2 group to 93 ± 3% in DMS group (Fig. 5E, P < 0.01). With MsrA shRNA, DMS showed little effects on the cell viability under oxidative stress (70 ± 4% in H2O2 model group vs. 78 ± 4% in DMS group). The protective effect of DMS on lipid peroxidation was also abolished, which resembled the findings in the H2O2‐induced cell death. As shown in Fig. 5F, the MDA content of DMS group (162 ± 9%) showed no difference with that in H2O2 model group (160 ± 7%).