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Oct-2 Transcription Factor Binding Activity and Expression Up-Regulation in Rat Cerebral Ischaemia is Associated with a Diminution of Neuronal Damage In Vitro

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Abstract

Brain plasticity provides a mechanism to compensate for lesions produced as a result of stroke. The present study aims to identify new transcription factors (TFs) following focal cerebral ischaemia in rat as potential therapeutic targets. A transient focal cerebral ischaemia model was used for TF-binding activity and TF–TF interaction profile analysis. A permanent focal cerebral ischaemia model was used for the transcript gene analysis and for the protein study. The identification of TF variants, mRNA analysis, and protein study was performed using conventional polymerase chain reaction (PCR), qPCR, and Western blot and immunofluorescence, respectively. Rat cortical neurons were transfected with small interfering RNA against the TF in order to study its role. The TF-binding analysis revealed a differential binding activity of the octamer family in ischaemic brain in comparison with the control brain samples both in acute and late phases. In this study, we focused on Oct-2 TF. Five of the six putative Oct-2 transcript variants are expressed in both control and ischaemic rat brain, showing a significant increase in the late phase of ischaemia. Oct-2 protein showed neuronal localisation both in control and ischaemic rat brain cortical slices. Functional studies revealed that Oct-2 interacts with TFs involved in important brain processes (neuronal and vascular development) and basic cellular functions and that Oct-2 knockdown promotes neuronal injury. The present study shows that Oct-2 expression and binding activity increase in the late phase of cerebral ischaemia and finds Oct-2 to be involved in reducing ischaemic-mediated neuronal injury.

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Acknowledgments

This work was partially supported by the Centre d’Innovació i Desenvolupament Empresarial (CIDEM) of the Generalitat de Catalunya (Grant No. RDITSCON07-1-0006), Grupo Ferrer Internacional SA, Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF) (PROFIT Grant No. CIT 090000-20008-11), Institut de Salud Carlos III (ISCIII) Grant Nos. FIS-PI070322, and ISCIII retics-RENEVAS-RD06/0026/0005 and RD07/0026/2002. Finally, thanks to Andrew Hughes for the linguistic revision of the manuscript.

Conflict of interest

The authors (Susanna Camós, Carme Gubern, Mónica Sobrado, Rocío Rodríguez, Víctor G Romera, María Ángeles Moro, Ignacio Lizasoain, Joaquín Serena, Judith Mallolas, and Mar Castellanos) declare that they have no conflict of interest.

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  1. Mónica Sobrado

    Present address: Servicio de Neurología, Instituto de Investigación Sanitaria, Hospital Universitario La Princesa, C/Diego de León, 62, 28006, Madrid, Spain

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  1. Servei de Neurologia, Institut d’Investigació Biomèdica de Girona (IdIBGi), Hospital Universitari de Girona Dr. Josep Trueta, Av. França s/n, 17007, Girona, Spain

    Susanna Camós, Carme Gubern, Rocío Rodríguez, Joaquín Serena, Judith Mallolas & Mar Castellanos

  2. Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Ciudad Universitaria, s/n, 28040, Madrid, Spain

    Mónica Sobrado, Víctor G. Romera, María Ángeles Moro & Ignacio Lizasoain

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Senior authors: Judith Mallolas and Mar Castellanos. Corresponding author: Judith Mallolas.

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Camós, S., Gubern, C., Sobrado, M. et al. Oct-2 Transcription Factor Binding Activity and Expression Up-Regulation in Rat Cerebral Ischaemia is Associated with a Diminution of Neuronal Damage In Vitro. Neuromol Med 16, 332–349 (2014). https://doi.org/10.1007/s12017-013-8279-1

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  • DOI: https://doi.org/10.1007/s12017-013-8279-1

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