TY - JOUR
T1 - Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide
AU - Kurokawa, Yuko
AU - Sekiguchi, Fumiko
AU - Kubo, Satoko
AU - Yamasaki, Yoshiko
AU - Matsuda, Sachi
AU - Okamoto, Yukari
AU - Sekimoto, Teruki
AU - Fukatsu, Anna
AU - Nishikawa, Hiroyuki
AU - Kume, Toshiaki
AU - Fukushima, Nobuyuki
AU - Akaike, Akinori
AU - Kawabata, Atsufumi
N1 - Funding Information:
This work was supported in part by “ Antiaging Center Project ” for Private Universities from Ministry of Education, Culture, Sports, Science and Technology, 2008–2012.
PY - 2011/11/4
Y1 - 2011/11/4
N2 - Hydrogen sulfide (H 2S), 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 2S 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 2S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.
AB - Hydrogen sulfide (H 2S), 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 2S 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 2S involves activation of the MEK/ERK pathway and some apoptotic mechanisms.
KW - Apoptosis
KW - Fetal cortical neuron
KW - Hydrogen sulfide (H S)
KW - MAP kinase
KW - Neurotoxicity
UR - http://www.scopus.com/inward/record.url?scp=80555122772&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2011.09.144
DO - 10.1016/j.bbrc.2011.09.144
M3 - 学術論文
C2 - 22001931
AN - SCOPUS:80555122772
SN - 0006-291X
VL - 414
SP - 727
EP - 732
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -