kn-93 and 1-1-diethyl-2-hydroxy-2-nitrosohydrazine

kn-93 has been researched along with 1-1-diethyl-2-hydroxy-2-nitrosohydrazine* in 1 studies

Other Studies

1 other study(ies) available for kn-93 and 1-1-diethyl-2-hydroxy-2-nitrosohydrazine

ArticleYear
Nitric oxide-mediated modulation of calcium/calmodulin-dependent protein kinase II.
    The Biochemical journal, 2008, Jun-01, Volume: 412, Issue:2

    The mechanisms of NO inhibition of CaMK [Ca(2+)/CaM (calmodulin)-dependent protein kinase] II activity were studied. In rat pituitary tumour GH3 cells, TRH [thyrotrophin (TSH)-releasing hormone]-stimulated phosphorylation of nNOS [neuronal NOS (NO synthase)] at Ser(847) was sensitive to an inhibitor of CaMKs, KN-93, and was enhanced by inhibition of nNOS with 7NI (7-nitroindazole). Enzyme activity of CaMKII following in situ treatment with 7NI was also increased. The in vitro activity of CaMKII was inhibited by co-incubation either with nNOS and L-arginine or with NO donors SNAP (S-nitroso-N-acetyl-DL-penicillamine) and DEA-NONOate [diethylamine-NONOate (diazeniumdiolate)]. Once inhibited by these treatments, CaMKII was observed to undergo full reactivation on the addition of a reducing reagent, DTT (dithiothreitol). In transfected cells expressing CaMKII and nNOS, treatment with the calcium ionophore A23187 further revealed nNOS phosphorylation at Ser(847), which was enhanced by 7NI and CaMKII S-nitrosylation. Mutated CaMKII (C6A), in which Cys(6) was substituted with an alanine residue, was refractory to 7NI-induced enhancement of nNOS phosphorylation or to CaMKII S-nitrosylation. Furthermore, we could identify Cys(6) as a direct target for S-nitrosylation of CaMKII using MS. In addition, treatment with glutamate caused an increase in CaMKII S-nitrosylation in rat hippocampal slices. This glutamate-induced S-nitrosylation was blocked by 7NI. These results suggest that inactivation of CaMKII mediated by S-nitrosylation at Cys(6) may contribute to NO-induced neurotoxicity in the brain.

    Topics: Animals; Benzylamines; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cell Line, Tumor; Cysteine; Enzyme Activation; Hippocampus; Hydrazines; Indazoles; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase Type I; Protein Kinase Inhibitors; Rats; S-Nitroso-N-Acetylpenicillamine; Serine; Sulfonamides; Thyrotropin-Releasing Hormone

2008