TY - JOUR
T1 - Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomics
AU - Santos, Ana Isabel
AU - Lourenço, Ana Sofia
AU - Simão, Sónia
AU - Marques da Silva, Dorinda
AU - Santos, Daniela Filipa
AU - Onofre de Carvalho, Ana Paula
AU - Pereira, Ana Catarina
AU - Izquierdo-Álvarez, Alicia
AU - Ramos, Elena
AU - Morato, Esperanza
AU - Marina, Anabel
AU - Martínez-Ruiz, Antonio
AU - Araújo, Inês Maria
N1 - Funding: The authors acknowledge the kind gift of HC7 cells by Dr. Fred H. Gage (The Salk Institute for Biological Studies). The excellent assistance of Pedro Marques Vilela in graphical artwork is acknowledged by the authors. Ana Santos and Ana Lourenço were supported by Foundation for Science and Technology, I.P. (FCT, Portugal; fellowships SFRH/BD/ 77903/2011 and SFRH/BD/79308/2011) and are PhD students of the PhD programme in Biomedical Sciences of the University of Algarve. Antonio Martínez-Ruiz is supported by the ISCIII from the Spanish Government (IS3SNS programme, partially funded by FEDER/ERDF). Inês Araújo is supported by FEDER/ERDF funds via Programa Operacional Factores de Competitividade (COMPETE), by national funds via FCT (grants PTDC/NEU-OSD/0473/2012, PTDC/QUI-QFI/ 29319/2017) and by regional funds via CRESC ALGARVE 2020 (grant UID/BIM/04773/2019), by the Algarve Biomedical Center (ABC) and Loulé Municipality. This work was supported by the COST action BM1005 (ENOG: European Network on Gasotransmitters), by the Spanish Government (grants PS09/00101, PI12/00875 and PI15/ 00107 from ISCIII and RTI2018-094203-B-I00 from AEI; co-financed by FEDER/ERDF) and by the Spanish-Portuguese Integrated Action grant PRI-AIBPT-2011-1015/E-10/12. The Proteomics Service of the CBMSO is a member of ProteoRed (PRB3-ISCIII), and is supported by grant PT13/0001/0024 of Spanish Government (cofinanced by FEDER/ ERDF).
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - Hippocampus
KW - Neural stem cells
KW - Neurogenesis
KW - Nitric oxide
KW - S-nitrosylation
KW - Seizures
UR - http://www.scopus.com/inward/record.url?scp=85079639048&partnerID=8YFLogxK
U2 - 10.1016/j.redox.2020.101457
DO - 10.1016/j.redox.2020.101457
M3 - Article
C2 - 32088623
AN - SCOPUS:85079639048
VL - 32
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
M1 - 101457
ER -