title: p38 MAP kinase and ERK play an important role in nitric oxide-induced apoptosis of the mouse embryonic stem cells.
abstract: 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.
authors.affiliation: Bio-energy Research Institute, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Jin-Ha
authors.initials: JH
authors.lastname: Lee
authors.forename: Sang-Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Sun-Hun
authors.initials: SH
authors.lastname: Kim
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Kim
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D007093:Imidazoles; D020030:Nitric Oxide Donors; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D009599:Nitroprusside; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases; C093642:SB 203580