uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Biphasic onset of splenic apoptosis following hemorrhagic shock: critical implications for Bax, Bcl-2, and Mcl-1 proteins
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Show others and affiliations
2008 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 1, p. R8-Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immune functions. METHODS: Male C57BL-6 mice were subjected to sham operation or resuscitated HS. At t = 0 hours, t = 24 hours, and t = 72 hours, mice were euthanized and the spleens were removed and evaluated for apoptotic changes via DNA fragmentation, caspase activities, and activation of both extrinsic and intrinsic apoptotic pathways. Spleens from untreated mice were used as control samples. RESULTS: HS was associated with distinct lymphocytopenia as early as t = 0 hours after hemorrhage without regaining baseline levels within the consecutive 72 hours when compared with sham and control groups. A rapid activation of splenic apoptosis in HS mice was observed at t = 0 hours and t = 72 hours after hemorrhage and predominantly confirmed by increased DNA fragmentation, elevated caspase-3/7, caspase-8, and caspase-9 activities, and enhanced expression of intrinsic mitochondrial proteins. Accordingly, mitochondrial pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were inversely expressed within the 72-hour observation period, thereby supporting significant pro-apoptotic changes. Solely at t = 24 hours, expression of the anti-apoptotic Mcl-1 protein shows a significant increase when compared with sham-operated and control animals. Furthermore, expression of extrinsic death receptors were only slightly increased. CONCLUSION: Our data suggest that HS induces apoptotic changes in spleen through a biphasic caspase-dependent mechanism and imply a detrimental imbalance of pro- and anti-apoptotic mitochondrial proteins Bax, Bcl-2, and Mcl-1, thereby promoting post-traumatic immunosuppression.

Place, publisher, year, edition, pages
2008. Vol. 12, no 1, p. R8-
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-113180DOI: 10.1186/cc6772PubMedID: 18211685OAI: oai:DiVA.org:uu-113180DiVA, id: diva2:290083
Available from: 2010-01-26 Created: 2010-01-26 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

fulltext(862 kB)158 downloads
File information
File name FULLTEXT01.pdfFile size 862 kBChecksum SHA-512
c913e903da5b621fa85235d8edb75f9db7fca5dcd18c3f0dc777152727c99c2665141a1f7ac57bf72b6125a09e115cad6c3c560b91390d5b285dec3c25fc493e
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records BETA

Robinson, Yohan

Search in DiVA

By author/editor
Robinson, Yohan
By organisation
Orthopaedics
In the same journal
Critical Care
Surgery

Search outside of DiVA

GoogleGoogle Scholar
Total: 158 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 512 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf