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

Ana Isabel Santos, Ana Sofia Lourenço, Sónia Simão, Dorinda Marques da Silva, Daniela Filipa Santos, Ana Paula Onofre de Carvalho, Ana Catarina Pereira, Alicia Izquierdo-Álvarez, Elena Ramos, Esperanza Morato, Anabel Marina, Antonio Martínez-Ruiz, Inês Maria Araújo

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Abstract

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.

Original languageEnglish
Article number101457
JournalRedox Biology
Volume32
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • Hippocampus
  • Neural stem cells
  • Neurogenesis
  • Nitric oxide
  • S-nitrosylation
  • Seizures

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