دورية أكاديمية
S-glutathionylation exerts opposing roles in the regulation of STAT1 and STAT3 signaling in reactive microglia
| العنوان: | S-glutathionylation exerts opposing roles in the regulation of STAT1 and STAT3 signaling in reactive microglia |
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| المؤلفون: | Butturini, Elena, Cozzolino, Flora, Boriero, Diana, Carcereri de Prati, Alessandra, Monti, Maria, Rossin, Michele, Canetti, Diana, Cellini, Barbara, Pucci, Piero, Mariotto, Sofia |
| المساهمون: | Butturini, Elena, Cozzolino, Flora, Boriero, Diana, Carcereri de Prati, Alessandra, Monti, Maria, Rossin, Michele, Canetti, Diana, Cellini, Barbara, Pucci, Piero, Mariotto, Sofia |
| سنة النشر: | 2018 |
| المجموعة: | IRIS Università degli Studi di Perugia |
| مصطلحات موضوعية: | Oxidative stre, S-glutathionylation, STAT1, STAT3, Biochemistry, Physiology (medical) |
| الوصف: | STAT1 and STAT3 are two transcription factors involved in a lot of cellular functions such as immune response, proliferation, apoptosis, and cell survival. A number of literature evidences described a yin-yang relationship between activation of STAT1 and STAT3 in neurodegenerative disorders where STAT1 exerts a pro-apoptotic effect whereas STAT3 shows neuroprotective properties through the inhibition of apoptosis. Although the role of oxidative-stress in the pathogenesis of neurodegeneration is clearly described, its influence in the regulation of these pathways is poorly understood. Herein, we demonstrate that H2O2 rapidly induces phosphorylation of STAT1 whereas it is not able to influence phosphorylation of STAT3 in mouse microglia BV2 cells. The analysis of the molecular mechanism of STATs signaling reveals that H2O2 induces S-glutathionylation of both STAT1 and STAT3. The same post-translational event exerts an opposing role in the regulation of STAT1 and STAT3 signaling. These data not only confirm redox sensibility of STAT3 signaling but also reveal for the first time that STAT1 is susceptible to redox regulation. A deep study of the molecular mechanism of STAT1 redox regulation, identifies Cys324 and Cys492 as the main targets of S-glutathionylation and confirms that S-glutathionylation does not impair JAK2 mediated STAT1 tyrosine phosphorylation. These results demonstrate that both phosphorylation and glutathionylation contribute to activation of STAT1 during oxidative stress and underline that the same post-translation event exerts an opposing role in the regulation of STAT1 and STAT3 signaling in microglia cells. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/29427792; info:eu-repo/semantics/altIdentifier/wos/WOS:000427420600019; volume:117; firstpage:191; lastpage:201; numberofpages:11; journal:FREE RADICAL BIOLOGY & MEDICINE; http://hdl.handle.net/11391/1428853Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85041807266; www.elsevier.com/locate/freeradbiomed |
| DOI: | 10.1016/j.freeradbiomed.2018.02.005 |
| الإتاحة: | https://doi.org/10.1016/j.freeradbiomed.2018.02.005Test http://hdl.handle.net/11391/1428853Test |
| رقم الانضمام: | edsbas.1D328F4F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.freeradbiomed.2018.02.005 |
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