Thioredoxin 1 and glutaredoxin 2 contribute to maintain the phenotype and integrity of neurons following perinatal asphyxia.
BACKGROUND
Thioredoxin (Trx) family proteins are crucial mediators of cell functions via regulation of the thiol redox state of various key proteins and the levels of the intracellular second messenger hydrogen peroxide. Their expression, localization and functions are altered in various pathologies. Here, we have analyzed the impact of Trx family proteins in neuronal development and recovery, following hypoxia/ischemia and reperfusion.


METHODS
We have analyzed the regulation and potential functions of Trx family proteins during hypoxia/ischemia and reoxygenation of the developing brain in both an animal and a cellular model of perinatal asphyxia. We have analyzed the distribution of 14 Trx family and related proteins in the cerebellum, striatum, and hippocampus, three areas of the rat brain that are especially susceptible to hypoxia. Using SH-SY5Y cells subjected to hypoxia and reoxygenation, we have analyzed the functions of some redoxins suggested by the animal experiment.


CONCLUSIONS
We have described/discovered a complex, cell-type and tissue-specific expression pattern following the hypoxia/ischemia and reoxygenation. Particularly, Grx2 and Trx1 showed distinct changes during tissue recovery following hypoxia/ischemia and reoxygenation. Silencing of these proteins in SH-SY5Y cells subjected to hypoxia-reoxygenation confirmed that these proteins are required to maintain the normal neuronal phenotype.


CONCLUSIONS
These findings demonstrate the significance of redox signaling in cellular pathways. Grx2 and Trx1 contribute significantly to neuronal integrity and could be clinically relevant in neuronal damage following perinatal asphyxia and other neuronal disorders.
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina.
Juan Ignacio
JI
Romero
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
Eva-Maria
EM
Hanschmann
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
Manuela
M
Gellert
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
Susanne
S
Eitner
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina.
Mariana Inés
MI
Holubiec
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina; Facultat d'Educació, Psicologia i Treball Social Universitat de Lleida Av. de l'Estudi General, 4, 25001 Lleida, Spain.
Eduardo
E
Blanco-Calvo
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
Christopher Horst
CH
Lillig
Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini" (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ, Ciudad de Buenos Aires, Argentina; Departamento de Biología, UAJFK, C1197AAR, Ciudad de Buenos Aires, Argentina. Electronic address: franciscocapani@hotmail.com.
Francisco
F
Capani
D000818:Animals; D001238:Asphyxia Neonatorum / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
C516008:GLRX2 protein, human; C516010:Glrx2 protein, rat; D054477:Glutaredoxins; C491203:TXN protein, human; C495697:Txn1 protein, rat; D013879:Thioredoxins; D010100:Oxygen
Common carotid artery occlusion; Hypoxia; Perinatal asphyxia; Reoxygenation; Thioredoxin family of proteins