Cell signaling mediated by nitrated cyclic guanine nucleotide

S-Guanylation Proteomics for Redox-Based Mitochondrial Signaling

“…8-Nitro-cGMP is the first known endogenously formed electrophilic nucleotide (3,12,18,36,48). 8-Nitro-cGMP reacts with protein thiols to induce a unique PTM, protein Sguanylation (3,12,36).…”

“…Accumulating evidence has also suggested that ROS are important for regulating various cellular functions via redox-based cellular signaling (7,10,11,16,49). Electrophiles such as oxidized/nitrated lipids and nitrated nucleotides formed as a result of ROS metabolism could act as second messengers in redox signaling (1,3,35,37).…”

Formation, signaling functions, and metabolisms of nitrated cyclic nucleotide

“…Accordingly, S-guanylation is apparently stable and produces irreversible sulfhdryl modifications, in contrast to other NO-mediated sulfhydryls modifications such as S-nitrosylation [35] and S-nitroalkylation by nitrofatty acids [36]. Kinetic analyses indicate that chemical reactivity of 8-nitro-cGMP with cysteine thiols is moderate compared with that of other biological electrophiles [3,4,37]. For instance, the reaction rate constants for glutathione (GSH) at pH 7.4 and 37°C are 0.03, 0.7, 1.3 183, and 355 M -1 s -1 for 8-nitro-cGMP, 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ), 4-hydroxy-2-nonenal (HNE), nitrooleic acid, and nitrolinoleic acid, respectively.…”

“…This post-translational modification (PTM) by 8-nitro-cGMP via cGMP adduction is named protein S-guanylation. Accumulating evidence has suggested the occurrence of S-guanylation on proteins that critically involved in the regulation of cellular responses to oxidative, metabolic or environmental stress [4][5][6]. Examples in- clude protein S-guanylation of Kelch-like ECH-associated protein 1 (Keap1) [3,7], H-Ras [8] and mitochondrial heat shock proteins [9].…”

Antioxidant Adaptive Response of Malignant Glioma Related to Resistance to Antitumor Treatment

“…8-Nitro-cGMP is the first known endogenously formed electrophilic nucleotide Fujii et al, 2010;Saito et al, 2008;Sawa et al, 2007;Zaki et al, 2009]. Because of its electrophilic characteristics, 8-nitro-cGMP reacts with cysteine residues in proteins, particularly residues with low pK a values that facilitate deprotonation of those residues to form a cysteine thiolate anion [Ahmed et al, 2011b;Akaike et al, 2010;Sawa et al, 2010]. Reaction of 8-nitro-cGMP with the thiolate anion results in cGMP adduction to the cysteine residue, a process called "protein S-guanylation" (Fig.…”