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Overexpression of HSP10 in transgenic mice protects skeletal muscle against endotoxic shock‐induced loss of force generation
Author(s) -
Kayani Anna Charlotte,
Routley Claire,
Douramani Maria Touramani,
Dillmann Wolfgang,
Mestril Ruben,
Jackson Malcolm
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1078.37
Subject(s) - sepsis , skeletal muscle , endotoxic shock , wasting , heat shock protein , shock (circulatory) , medicine , hsp70 , endocrinology , tumor necrosis factor alpha , septic shock , chemistry , biochemistry , gene
Impairment of skeletal muscle function and wasting are consistent and severe features of sepsis and are associated with poor outcome. The rate of loss of muscle in septic patients with multiple organ failure is between 2 and 4% per day. We have demonstrated that overexpression of the mitochondrial chaperone HSP10 prevents age related loss of maximum force generation and cross sectional area and we hypothesised that HSP10 would be beneficial in preventing the loss of muscle function during sepsis. WT and HSP10 overexpressor mice were treated with LPS at 2.5mg/Kg and maximum force generation of EDL muscles was measured after 24hrs. Overexpression of HSP10 resulted in significant protection against LPS induced loss of maximum force generation compared with WT mice and additionally protected against the systemic symptoms of endotoxic shock observed in WT mice. HSP10 overexpression significantly reduced serum protein levels and muscle mRNA content of TNF‐α and IL‐6 compared with WT mice. Muscle fibres were isolated from FDB muscles and treated with LPS at 1μg/ml for 5hr. A significant reduction in the TNF‐α release was observed from fibres from HSP10 overexpressor mice compared with WT. These data suggest that anti‐inflammatory effects of HSP10 protect against the loss of maximum force and the severity of systemic illness during endotoxic shock and therefore provides a potential therapeutic target in sepsis. Funded by MRC.