Referenced in: none

Automatically associated channels: Slo1

Title: Involvement of ERK in NMDA receptor-independent cortical neurotoxicity of hydrogen sulfide.

Authors: Yuko Kurokawa, Fumiko Sekiguchi, Satoko Kubo, Yoshiko Yamasaki, Sachi Matsuda, Yukari Okamoto, Teruki Sekimoto, Anna Fukatsu, Hiroyuki Nishikawa, Toshiaki Kume, Nobuyuki Fukushima, Akinori Akaike, Atsufumi Kawabata

Journal, date & volume: Biochem. Biophys. Res. Commun., 2011 Nov 4 , 414, 727-32

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22001931

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.