Academic Journal
S100B protein activates a RAGE‐dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis
| العنوان: | S100B protein activates a RAGE‐dependent autocrine loop in astrocytes: implications for its role in the propagation of reactive gliosis |
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| المؤلفون: | Villarreal, Alejandro, Seoane, Rocío, González Torres, Agustina, Rosciszewski, Gerardo, Angelo, Maria Florencia, Rossi, Alicia, Barker, Philip A., Ramos, Alberto Javier |
| المساهمون: | CONICET, ANPCYT, UBACYT, CIHR |
| المصدر: | Journal of Neurochemistry ; volume 131, issue 2, page 190-205 ; ISSN 0022-3042 1471-4159 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2014 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Extracellular S100B dramatically increases after brain injury. While low S100B levels are neuroprotective, micromolar S100B levels have shown in vitro to activate microglia and facilitate neuronal death. In astrocytes, S100B exposure activates nuclear factor kappa B (NF‐κB) and induces pro‐inflammatory mediators. On microglia and neurons S100B effects are essentially mediated by receptor for advanced glycation end products (RAGE)/NF‐κB, but it is not clear if these intracellular cascades are activated by different S100B levels in astrocytes and whether increased extracellular S100B is sufficient to induce reactive gliosis. A better understanding of these pathways is essential for developing successful strategies to preserve the beneficial S100B effects after brain injury. Here, we show that microglia‐depleted cultured astrocytes exposed to S100B mimicked several features of reactive gliosis by activating RAGE/Rac‐1‐Cdc42, RAGE/Erk‐Akt or RAGE/NF‐κB‐dependent pathways. S100B effects include RAGE/Rac1‐Cdc42‐dependent astroglial hypertrophy and facilitation of migration as well as increased mitosis. S100B exposure improved the astrocytic survival to oxidative stress, an effect that requires Erk/Akt. S100B also activates NF‐κB in a dose‐dependent manner; increases RAGE proximal promoter transcriptional activity and augmented endogenous RAGE expression. S100B‐exposed astrocytes showed a pro‐inflammatory phenotype with expression of Toll‐like receptor 2 (TLR 2), inducible nitric oxide synthase ( iNOS ) and interleukin 1‐beta (IL‐1β), and facilitated neuronal death induced by oxygen‐glucose deprivation. In vivo , intracerebral infusion of S100B was enough to induce an astroglial reactive phenotype. Together, these findings demonstrate that extracellular S100B in the micromolar level activates different RAGE‐dependent pathways that turn astrocytes into a pro‐inflammatory and neurodegenerative phenotype. image We propose that S100B turns astrocytes into a reactive phenotype in a RAGE‐dependent manner but ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/jnc.12790 |
| الاتاحة: | http://dx.doi.org/10.1111/jnc.12790 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjnc.12790 https://onlinelibrary.wiley.com/doi/pdf/10.1111/jnc.12790 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.F8583AFC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/jnc.12790 |
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