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Biochim Biophys Acta. 2015 Jun;1850(6):1274-85. doi: 10.1016/j.bbagen.2015.02.015. Epub 2015 Feb 28.

Thioredoxin 1 and glutaredoxin 2 contribute to maintain the phenotype and integrity of neurons following perinatal asphyxia.

Author information

1
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.
2
Institute for Medical Biochemistry and Molecular Biology, Universitätsmedizin Greifswald, Ernst-Moritz-Arndt-Universität Greifswald, 17475 Greifswald, Germany.
3
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.
4
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.

Abstract

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.

RESULTS AND 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.

GENERAL SIGNIFICANCE:

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.

KEYWORDS:

Common carotid artery occlusion; Hypoxia; Perinatal asphyxia; Reoxygenation; Thioredoxin family of proteins

PMID:
25735211
DOI:
10.1016/j.bbagen.2015.02.015
[Indexed for MEDLINE]

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