title: Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide.
abstract: Hydrogen sulfide (H(2)S), a gasotransmitter, exerts both neurotoxicity and neuroprotection, and targets multiple molecules including NMDA receptors, T-type calcium channels and NO synthase (NOS) that might affect neuronal viability. Here, we determined and characterized effects of NaHS, an H(2)S donor, on cell viability in the primary cultures of mouse fetal cortical neurons. NaHS caused neuronal death, as assessed by LDH release and trypan blue staining, but did not significantly reduce the glutamate toxicity. The neurotoxicity of NaHS was resistant to inhibitors of NMDA receptors, T-type calcium channels and NOS, and was blocked by inhibitors of MEK, but not JNK, p38 MAP kinase, PKC and Src. NaHS caused prompt phosphorylation of ERK and upregulation of Bad, followed by translocation of Bax to mitochondria and release of mitochondrial cytochrome c, leading to the nuclear condensation/fragmentation. These effects of NaHS were suppressed by the MEK inhibitor. Our data suggest that the NMDA receptor-independent neurotoxicity of H(2)S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.
authors: Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
authors: Yuko
authors: Y
authors: Kurokawa
authors: Fumiko
authors: F
authors: Sekiguchi
authors: Satoko
authors: S
authors: Kubo
authors: Yoshiko
authors: Y
authors: Yamasaki
authors: Sachi
authors: S
authors: Matsuda
authors: Yukari
authors: Y
authors: Okamoto
authors: Teruki
authors: T
authors: Sekimoto
authors: Anna
authors: A
authors: Fukatsu
authors: Hiroyuki
authors: H
authors: Nishikawa
authors: Toshiaki
authors: T
authors: Kume
authors: Nobuyuki
authors: N
authors: Fukushima
authors: Akinori
authors: A
authors: Akaike
authors: Atsufumi
authors: A
authors: Kawabata
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013440:Sulfides / Q000633:toxicity; D015854:Up-Regulation; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
chemical_list: C494820:Bad protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D013440:Sulfides; D051025:bcl-Associated Death Protein; C025451:sodium bisulfide; D002118:Calcium; D006862:Hydrogen Sulfide