title: Modulation of the unfolded protein response during hepatocyte and cardiomyocyte apoptosis in trauma/hemorrhagic shock.
abstract: Trauma with hemorrhagic shock (T/HS), has been shown to result in liver injury marked by hepatocyte apoptosis and heart failure marked by cardiomyocyte apoptosis, both of which we have shown to be prevented by IL-6 administration at resuscitation, and Stat3 largely mediated this. As specific mediators have not been delineated, we investigated the unfolded protein response (UPR), which, with marked activation, can lead to apoptosis. Prior studies of hepatic and cardiac injury examined limited repertoires of UPR elements, making it difficult to assess the role of the UPR in T/HS. This study describes the first global examination of the UPR transcriptome in the liver and heart following T/HS, demonstrating organ-specific UPR transcriptome changes. The non-canonical UPR chaperone, Hsp70, was most dysregulated following T/HS and may contribute to hepatocyte protection via an IL-6-mediated pathway, identifying a potential new therapeutic strategy to prevent hepatocyte death and organ dysfunction in T/HS.
authors: Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors: Stephen A
authors: SA
authors: Thacker
authors: Prema
authors: P
authors: Robinson
authors: Adam
authors: A
authors: Abel
authors: David J
authors: DJ
authors: Tweardy
mesh_terms: D000818:Animals; D017209:Apoptosis; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012151:Resuscitation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology; D012774:Shock, Traumatic / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome; D056811:Unfolded Protein Response
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor
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