Protein S-nitrosylation

S. H., Protein S-nitrosylation a physiological signal for neuronal nitric oxide, Nat. Cell Biol. (2001), p.3193-3197... 

Heme does, however, not seem to be required for protein S-nitrosylation to occur. The precise chemistry is unsettled Figure 11.7a gives one hypothetic reaction scheme. Here, S-nitrosylation generates one equivalent of superoxide, which in turn (and particularly so at high concentrations of NO) may react with another molecule of NO to generate peroxynitrite. Peroxynitrite is very reactive and may oxidize other sites in proteins, or it may give rise to 0-nitrosy-lation of protein tyrosine side chains. 

Does S-nitrosylation really have a regulatory role in the cell This raises the question how specific protein S-nitrosylation might be. From the non-enz5miatic nature of the chemistry discussed above, one might expect S-nitro-sylation to be a very indiscriminate process, which would amount to a lot of noise in the signal - and thus, probably. 

Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS. Protein S-nitrosylation purview and parameters. Nat. Rev. Mol. Cell Biol. 2005 6 150-166. 

Hattori H, Wasterlain CG (1990) Excitatory amino acids in the developing brain ontogeny, plasticity, and excitotoxicity. Pediatr Neurol 6 219-228 He J, Wang T, Wang P, Han P, Chen C (2007) A novel mechanism underlying the susceptibility of neuronal cells to nitric oxide the occurrence and regulation of protein S-nitrosylation is the checkpoint. J Neurochem 102 1863-1874... 

Hoffmann, J., Haendeler, J., Zeiher, A.M., and Dimmeler, S. (2001). TNFalpha and oxLDL reduce protein S-nitrosylation in endothelial cells. J. Biol. Chem. 276,41383-41387. 

Han P, Zhou X, Huang B et al (2008) On-gel fluorescent visualization and the site identification of S-nitrosylated proteins. Anal Biochem 377 150-155... 

Martinez-Ruiz, A., Lamas, S., Detection and proteomic identification of S-nitrosylated proteins in endothelial cells, Arch Biochem Biophys. 423 (2004), p. 192-199... 

Micromolar quantities of RNS are generated primarily by nitric oxide synthase 2 (NOS2), an enzyme that is up-regulated during colon-cancer progression. As discussed below, deoxycholate (DOC), a hydrophobic secondary bile acid, activates the redox-sensitive transcription factor NF-kB, resulting in increased levels of NOS2 and enhanced S-nitrosylation of proteins. Additional sources of bile-acid-induced ROS and RNS are also likely. ... 

M. Dall Agnol, C. Bernstein, H. Bernstein, H. Garewal and C. M. Payne, Identifieation of S-nitrosylated proteins after chronic exposure of colon epithelial cells to deoxycholate, Proteomics, 2006, 6(5), 1654. 

Hemoglobin was the first protein for which a regulatory action of S-nitrosylation has been clearly shown (Lia et al., 1996 Fig. 6.15). Hemoglobin (Hb) is a tetramer, composed of two a and two P chains. In man, each chain has a heme system and the P chains... 

Stamler, j. S., Simon, D. 1., Osborne, J. A., Mullins, M. E., Jaraki, O., Michel, T., Singel, D. J., and Loscalzo, j. (1992b). S-Nitrosylation of proteins with nitric oxide Synthesis and characterization of biologically active compounds. Proc. Natl. Acad. Sci. U.S.A. 89, 444-448. 

Nitrosyl complexes of both S = and S = are common. The S = nitrosyl complexes or iron and copper have slightly anisotropic g tensors (Ag/g < 2) with the anisotropy provided primarily by contributions of orbital angular momentum from the metal d orbitals. As an example, we consider the model proposed by Kon and Katakoa (1969) for ferroprotoheme-NO complexes, which is also applicable to the ferrous-nitrosyl complexes of heme proteins. In the complexes studied by these workers, the axial ligands are a nitrogenous base and NO. They proposed that the unpaired electron resides primarily in the metal d z orbital. The spin-orbit coupling would then mix contributions from the d, and dy orbitals. 

This mechanism may account partially for the stimulatory action of NO on transmitter release in hippocampal synapses (Schuman et al. 1994). Last but not least, NO may modulate cellular functions by S-nitrosylation of various proteins. For example, S-nitrosylation of nuclear proteins associated with cAMP response element (CRE) binding protein is involved in regulation of its DNA binding and, hence, CRE-mediated gene expression (Riccio et al. 2006). S-nitrosylation has also been reported to modify the function of various ion channels (Broillet and Firestein 1996, 1997 Xu et al. 1998 Jaffrey et al. 2001). 

Xu L, Eu JP, Meissner G, Stamler JS (1998) Activation of the cardiac calcium release channel (ryanodine receptor) by poly-S-nitrosylation. Science 279 234-7 Xue J, Wang X, Malladi CS, Kinoshita M, Milbum PJ, Lengyel I, Rostas JA, et al. (2000) Phosphorylation of a new brain-specific septin, G-septin, by cGMP-dependent protein kinase. J Biol... 

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