p38 MAP kinase and ERK play an important role in nitric oxide-induced apoptosis of the mouse embryonic stem cells

Previous study showed that nitric oxide (NO) induces apoptosis in mouse embryonic stem (mES) cells, but the precise mechanism governing NO-induced apoptosis in mES remains unclear. This study investigated the mechanism of NO-induced apoptosis of mES cells via MAP kinase signaling pathway. Sodium nitroprusside (SNP), a NO donor, induced apoptosis in mES cells with enhanced production of reactive oxygen species (ROS). In addition, treatment with SNP induced the activation of caspase-3, -8 and -9 as well as mitogen-activated protein (MAP) kinases (JNK, p38 MAP kinase and ERK). However, pretreatment with the p38 MAP kinase inhibitor SB203580 and ERK inhibitor U0126 attenuated NO-induced cell toxicity, ROS production, and caspase-3 activation. Moreover, SB203580 inhibited the translocation of Bax from the cytosol to the mitochondria. Taken together, these results suggest that NO-induced apoptosis in mES cells was mediated through p38 MAP kinase/ERK signaling pathway by triggering caspases activation and Bax translocation from the cytosol to the mitochondria.

► Nitric oxide (NO) induces apoptosis in mouse embryonic stem cells (mESC). ► NO activated mitogen-activated protein (MAP) kinases in apoptosis of mESC. ► p38 MAP kinase regulated Bax translocation to the mitochondria in apoptosis of mESC. ► p38 MAP kinase is a key regulator of NO-induced apoptosis in mESC.