S -Nitrosylation Regulates Cell Survival and Death in the Central Nervous System
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ORIGINAL PAPER
S-Nitrosylation Regulates Cell Survival and Death in the Central Nervous System Yoshiki Koriyama1 · Ayako Furukawa1
Received: 23 March 2017 / Revised: 25 April 2017 / Accepted: 10 May 2017 © Springer Science+Business Media New York 2017
Abstract Nitric oxide (NO), which is produced from nitric oxide synthase, is an important cell signaling molecule that is crucial for many physiological functions such as neuronal death, neuronal survival, synaptic plasticity, and vascular homeostasis. This diffusible gaseous compound functions as an effector or second messenger in many intercellular communications and/or cell signaling pathways. Protein S-nitrosylation is a posttranslational modification that involves the covalent attachment of an NO group to the thiol side chain of select cysteine residues on target proteins. This process is thought to be very important for the regulation of cell death, cell survival, and gene expression in the central nervous system (CNS). However, there have been few reports on the role of protein S-nitrosylation in CNS disorders. Here, we briefly review specific examples of S-nitrosylation, with particular emphasis on its functions in neuronal cell death and survival. An understanding of the role and mechanisms underlying the effects of protein S-nitrosylation on neurodegenerative/neuroprotective events may reveal a novel therapeutic strategy for rescuing neurons in neurodegenerative diseases. Keywords Nitric oxide · S-Nitrosylation · CNS · Death · Survival
* Yoshiki Koriyama koriyama@suzuka‑u.ac.jp 1
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500‑3 Minamitamagaki, Suzuka 513‑8670, Japan
Introduction Nitric oxide (NO) is a gas that is freely permeable to the cellular plasma membrane; thus, it does not need a biological receptor to affect intracellular communication and/ or signal transduction mechanisms. NO has dual effects: low levels of NO that are produced under physiological conditions stimulate many normal intracellular signaling pathways, whereas high levels lead to cellular injury [1]. Several neuronal models have demonstrated the neuroprotective actions of NO. For example, in dorsal root ganglia neurons, NO protects neurons after peripheral nerve injury [2]. In a cerebellar granule cell model, serum deprivationinduced cell death was rescued by NO donors [3]. Another neuronal cell model of trophic factor deprivation in spinal cord motor neurons demonstrated that NO exerted its neuroprotective effects by regulating the cyclic guanosine monophosphate (cGMP)-dependent signaling pathway [4]. NO activated the phosphatidylinositol 3-kinase (PI3K)/Akt survival signaling pathway and promoted cell survival in a 6-hydroxydopamine (6-OHDA)-induced apoptotic neuronal model of rat pheochromocytoma PC12 cells [5]. In a previous study, we proposed that NO-activated protein kinase activity is involved in neuritogenesis [6]. Furthermore, an NO donor and cGMP analog promoted neurite outgrowth in PC12h cells, whereas an NO synth
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