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Glial proteome changes in response to moderate hypothermia

Identifieur interne : 001418 ( Main/Exploration ); précédent : 001417; suivant : 001419

Glial proteome changes in response to moderate hypothermia

Auteurs : Jong-Heon Kim ; Young-Eun Cho ; Minchul Seo ; Moon-Chang Baek ; Kyoungho Suk [Corée du Sud]

Source :

RBID : ISTEX:2A725C5EC375E84FF5E7AF35A8A17E97DD61ABEF

English descriptors

Abstract

Reactive glia plays a central role in neuroinflammation associated with secondary damage after brain injury. In order to understand the global effects of therapeutic hypothermia on glial activation and neuroinflammation, we performed proteomic profiling of glial cultures following inflammatory stimulation and hypothermic exposure. Primary mixed glial cultures prepared from mouse brains were stimulated with lipopolysaccharide and interferon‐γ under normothermic (37°C) or moderate hypothermic (29°C) conditions, and their proteome profiles were compared by LC‐ESI‐MS/MS. Differentially expressed proteins were determined by high‐throughput label‐free quantification. Under hypothermic conditions, 64 and 16 proteins were upregulated (≥1.5‐fold) and downregulated (≤ 0.7‐fold), respectively, compared to normothermic conditions. More importantly, hypothermia altered the abundance of 143 proteins that were either increased or decreased by inflammatory stimulation. The results were validated for several proteins (ICAM‐1, STAT‐1, YWHAB, and IFIT‐3) by Western blot analysis. Pathway and network analysis indicate that hypothermia influences various biological functions of glia such as molecular transport, cell movement, immune response, cell death, and stress response. In conclusion, moderate hypothermia seems to have a significant effect on the protein expression profiles of brain glia and possibly ensuing neuroinflammation. These proteins may be involved in the protective mechanism of hypothermia against brain injuries.

Url:
DOI: 10.1002/pmic.201200024


Affiliations:


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Le document en format XML

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<term>Cell death</term>
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<term>Therapeutic hypothermia</term>
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<div type="abstract">Reactive glia plays a central role in neuroinflammation associated with secondary damage after brain injury. In order to understand the global effects of therapeutic hypothermia on glial activation and neuroinflammation, we performed proteomic profiling of glial cultures following inflammatory stimulation and hypothermic exposure. Primary mixed glial cultures prepared from mouse brains were stimulated with lipopolysaccharide and interferon‐γ under normothermic (37°C) or moderate hypothermic (29°C) conditions, and their proteome profiles were compared by LC‐ESI‐MS/MS. Differentially expressed proteins were determined by high‐throughput label‐free quantification. Under hypothermic conditions, 64 and 16 proteins were upregulated (≥1.5‐fold) and downregulated (≤ 0.7‐fold), respectively, compared to normothermic conditions. More importantly, hypothermia altered the abundance of 143 proteins that were either increased or decreased by inflammatory stimulation. The results were validated for several proteins (ICAM‐1, STAT‐1, YWHAB, and IFIT‐3) by Western blot analysis. Pathway and network analysis indicate that hypothermia influences various biological functions of glia such as molecular transport, cell movement, immune response, cell death, and stress response. In conclusion, moderate hypothermia seems to have a significant effect on the protein expression profiles of brain glia and possibly ensuing neuroinflammation. These proteins may be involved in the protective mechanism of hypothermia against brain injuries.</div>
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