Involvement of S-nitrosylation of actin in inhibition of neurotransmitter release by nitric oxide
12 pages
English

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Involvement of S-nitrosylation of actin in inhibition of neurotransmitter release by nitric oxide

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12 pages
English
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Description

The role of the diffusible messenger nitric oxide (NO) in the regulation of pain transmission is still a debate of matter, pro-nociceptive and/or anti-nociceptive. S -Nitrosylation, the reversible post-translational modification of selective cysteine residues in proteins, has emerged as an important mechanism by which NO acts as a signaling molecule. The occurrence of S -nitrosylation in the spinal cord and its targets that may modulate pain transmission remain unclarified. The "biotin-switch" method and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were employed for identifying S -nitrosylated proteins. Results Here we show that actin was a major protein S -nitrosylated in the spinal cord by the NO donor, S -nitroso- N -acetyl-DL-penicillamine (SNAP). Interestingly, actin was S -nitrosylated, more in the S2 fraction than in the P2 fraction of the spinal homogenate. Treatment of PC12 cells with SNAP caused rapid S -nitrosylation of actin and inhibited dopamine release from the cells. Just like cytochalasin B, which depolymerizes actin, SNAP decreased the amount of filamentous actin cytoskeleton just beneath the membrane. The inhibition of dopamine release was not attenuated by inhibitors of soluble guanylyl cyclase and cGMP-dependent protein kinase. Conclusion The present study demonstrates that actin is a major S -nitrosylated protein in the spinal cord and suggests that NO directly regulates neurotransmitter release by S -nitrosylation in addition to the well-known phosphorylation by cGMP-dependent protein kinase.

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Publié par
Publié le 01 janvier 2009
Nombre de lectures 6
Langue English

Extrait

Pga e 1fo1 (2apegum nr bet nor foaticnoitrup esops)
Research Involvement of S -nitrosylation of actin in inhibition of neurotransmitter rele ase by nitric oxide Jingshan Lu 1 , Tayo Katano 1 , Emiko Okuda-Ashitaka 1 , Yo Oishi 2 , Yoshihiro Urade 2 and Seiji Ito* 1
Address: 1 Department of Medical Chemistry, Kansai Medical University, Moriguchi, Japan and 2 Department of Molecula r Behavioral Biology, Osaka Bioscience Institute, Osaka, Japan Email: Jingshan Lu - lujing@takii.kmu.ac.jp; Tayo Katano - katanot@t akii.kmu.ac.jp; Emiko Okuda-Ashit aka - ashitaka@takii.kmu.ac.jp; Yo Oishi - oishi@obi.or.jp; Yoshihiro Urade - urade y@obi.or.jp; Seiji Ito* - ito@takii.kmu.ac.jp * Corresponding author
Open Access
Bio Med Central
Background of immune responses [1,2]. The major intracellular recep-Nitric oxide (NO) is produced from L-arginine by 3 iso- tor for NO is a soluble guanylyl cyclase that catalyzes the forms of NO synthase (NOS), i.e., neuronal NOS (NOS- synthesis of cGMP. This intracellular signaling molecule 1), inducible NOS (NOS-2), and endothelial NOS (NOS- modulates the activity of many targets in the cells includ-3); and it plays important roles in a wide variety of physi- ing cGMP-dependent protein kinase (cGK), ion channels, ological and pathophysiological processes such as neuro- and phosphodiesterases. In the central nervous system, transmission, regulation of vascular tone, and mediation NO is mainly produced by NOS-1 and has been impli-
Abstract Background:The role of the diffusible messenger nitr ic oxide (NO) in the regulation of pain transmission is still a deba te of matter, pro-nociceptiv e and/or anti-nociceptive. S -Nitrosylation, the reversible post-translation al modification of selective cysteine residues in proteins, has emerged as an important mechanism by which NO acts as a signaling molecule. The occurrence of S -nitrosylation in the spinal cord and its target s that may modulate pa in transmission remain unclarified. The "biotin-switch" method and matrix-assisted lase r desorption/ionization time-of-flight mass spectrometry were employed for identifying S -nitrosylated proteins. Results: Here we show that actin was a major protein S -nitrosylated in the spinal cord by the NO donor, S -nitroso-N -acetyl-DL-penicillamine (SNAP) . Interestingly, actin was S -nitrosylated, more in the S2 fraction than in the P2 fraction of th e spinal homogenate. Treatment of PC12 cells with SNAP caused rapid S -nitrosylation of actin and inhibited dopa mine release from the cells. Just like cytochalasin B, which depolymerizes actin, SNAP decreased the amount of filamentous actin cytoskeleton just beneath the me mbrane. The inhibition of dopa mine release was not attenuated by inhibitors of soluble guanylyl cyclase and cGMP-dependent protein kinase. Conclusion: The present study demonstrat es that actin is a major S -nitrosylated protein in the spinal cord and suggests that NO directl y regulates neurotransmitter release by S -nitrosylation in addition to the well-known phosphorylati on by cGMP-dependent protein kinase.
Published: 29 September 2009 Received: 16 June 2009 Accepte Molecular Pain 2009, 5 :58 doi:10.1186/1744-8069-5-58 d: 29 September 2009 This article is available from: http ://www.molecularpain.com/content/5/1/58 © 2009 Lu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orig inal work is properly cited.
Molecular Pain
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