Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion - PubMed (original) (raw)

. 2012 May;121(4):680-92.

doi: 10.1111/j.1471-4159.2012.07721.x. Epub 2012 Mar 28.

Gabriella Casalena, Jia Jia, Rukhsana Sultana, Eugenio Barone, Jian Cai, William M Pierce, Chiara Cini, Cesare Mancuso, Marzia Perluigi, Catherine M Davis, Nabil J Alkayed, D Allan Butterfield

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Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion

Fabio Di Domenico et al. J Neurochem. 2012 May.

Erratum in

Abstract

Signal transduction and activator of transcription-3 (STAT3) plays an important role in neuronal survival, regeneration and repair after brain injury. We previously demonstrated that STAT3 is activated in brain after cerebral ischemia specifically in neurons. The effect was sex-specific and modulated by sex steroids, with higher activation in females than males. In the current study, we used a proteomics approach to identify downstream proteins affected by ischemia in male and female wild-type (WT) and neuron-specific STAT3 knockout (KO) mice. We established four comparison groups based on the transgenic condition and the hemisphere analyzed, respectively. Moreover, the sexual variable was taken into account and male and female animals were analyzed independently. Results support a role for STAT3 in metabolic, synaptic, structural and transcriptional responses to cerebral ischemia, indeed the adaptive response to ischemia/reperfusion injury is delayed in neuronal-specific STAT3 KO mice. The differences observed between males and females emphasize the importance of sex-specific neuronal survival and repair mechanisms, especially those involving antioxidant and energy-related activities, often caused by sex hormones.

© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

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Figures

Figure 1

Figure 1

Representative 2D gel of protein identified, by mass spectrometry, with altered levels in WT (left) and STAT3 KO (right) female (top) and male (bottom) ipsilateral vs. contralateral proteomics comparison. O = altered proteins identified in WT animals; △ = altered proteins identified in neuronal-specific STAT3 KO animals;

Figure 2

Figure 2

Representative 2D gel of protein identified, by mass spectrometry, with altered levels in contralateral (left) and ipsilateral (right) female (top) and male (bottom) WT vs. neuronal-specific STAT3 KO proteomics comparison. O = altered proteins identified in contralateral hemisphere; △ = altered proteins identified in ipsilateral hemisphere;

Figure 3

Figure 3

Western blot image and relative graph bar of Pin-1 and β actin protein levels in WT and neuronal-specific STAT3 KO, ispsilateral and contralateral female samples; comparison between WT female ispilateral and neuronal-specific STAT3-KO female ipsilateral samples.

Figure 4

Figure 4

Interactome maps showing direct and indirect relationship between the proteins identified in this study with altered expression (yellow) in presence or absence of STAT3 in neuronal tissue; LEFT: direct and indirect interaction of all the proteins between them, with and trough STAT3, the green lines represent the direct interaction of identified protein and STAT3, the orange lines represents indirect interaction with STAT3 and direct and indirect interaction of the proteins between them; RIGHT: direct and indirect interactions of all the proteins between them without STAT3 (orange lines). A description of the interactome software is given in Materials and Methods.

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References

    1. Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene. 2000;19:2607–2611. - PubMed
    1. Alexander-Kaufman K, Harper C. Transketolase: observations in alcohol-related brain damage research. Int J Biochem Cell Biol. 2009;41:717–720. - PubMed
    1. Alkayed NJ, Goto S, Sugo N, Joh HD, Klaus J, Crain BJ, Bernard O, Traystman RJ, Hurn PD. Estrogen and Bcl-2: gene induction and effect of transgene in experimental stroke. J Neurosci. 2001;21:7543–7550. - PMC - PubMed
    1. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD. Gender-linked brain injury in experimental stroke. Stroke. 1998;29:159–165. discussion 166. - PubMed
    1. Alkayed NJ, Murphy SJ, Traystman RJ, Hurn PD, Miller VM. Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke. 2000;31:161–168. - PubMed

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