Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomics

Nitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S...

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Published in:	Redox biology Vol. 32; p. 101457
Main Authors:	Santos, Ana Isabel, Lourenço, Ana Sofia, Simão, Sónia, Marques da Silva, Dorinda, Santos, Daniela Filipa, Onofre de Carvalho, Ana Paula, Pereira, Ana Catarina, Izquierdo-Álvarez, Alicia, Ramos, Elena, Morato, Esperanza, Marina, Anabel, Martínez-Ruiz, Antonio, Araújo, Inês Maria
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-05-2020 Elsevier
Subjects:	Hippocampus Neural stem cells Neurogenesis Nitric oxide Research Paper S-nitrosylation Seizures Neural stem cells Neurogenesis Nitric oxide Hippocampus S-nitrosylation Seizures
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Summary:	Nitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S-nitrosylation. This post-translational modification consists in the formation of a nitrosothiol group (R–SNO) in cysteine residues, which can promote formation of other oxidative modifications in those cysteine residues. S-nitrosylation can regulate many physiological processes, including neuronal plasticity and neurogenesis. In this work, we aimed to identify S-nitrosylation targets of NO that could participate in neurogenesis. In NSC, we identified a group of proteins oxidatively modified using complementary techniques of thiol redox proteomics. S-nitrosylation of some of these proteins was confirmed and validated in a seizure mouse model of hippocampal injury and in cultured hippocampal stem cells. The identified S-nitrosylated proteins are involved in the ERK/MAPK pathway and may be important targets of NO to enhance the proliferation of NSC. [Display omitted] •Nitric oxide (NO) regulates neurogenesis, and increases proliferation of neural stem cells (NSC).•S-nitrosylation is a cysteine oxidation that acts as a relevant non-classical mechanism of NO signaling.•Cysteine oxidation targets were screened in NSC, confirming S-nitrosylation of several proteins.•S-nitrosylation of some of these targets was confirmed in cultured hippocampal stem cells.•S-nitrosylation of several proteins was observed in an in vivo model of hippocampal neurogenesis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1150-082 Lisboa, Portugal. AI Santos and AS Lourenço contributed equally to this work. Both authors act as equivalent co-senior authors and corresponding authors
ISSN:	2213-2317 2213-2317
DOI:	10.1016/j.redox.2020.101457