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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/H3179    most recent 01337.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Childs, E. W. Articles by Cao, X. Search for Related Content PubMed PubMed Citation Articles by Childs, E. W. Articles by Cao, X.

Apoptotic signaling induces hyperpermeability following hemorrhagic shock

Department of Surgery, Texas A&M University Health Science Center, College of Medicine and Scott & White Memorial Hospital, Temple, Texas

Submitted 7 December 2006 ; accepted in final form 14 February 2007

Hemorrhagic shock (HS) disrupts the endothelial cell barrier, resulting in microvascular hyperpermeability. Recent studies have also demonstrated that activation of the apoptotic signaling cascade is involved in endothelial dysfunction, which may result in hyperpermeability. Here we report involvement of the mitochondrial "intrinsic" pathway in microvascular hyperpermeability following HS in rats. HS resulted in the activation of the mitochondrial intrinsic pathway, as is evident from an increase in the proapoptotic Bcl-2 family member BAK, release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. This, along with the in vivo transfection of the proapoptotic peptide BAK (BH3), resulted in hyperpermeability (as visualized by intravital microscopy), release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. Conversely, transfection of the BAK (BH3) mutant had no effect on hyperpermeability. Together, these results demonstrate involvement of the mitochondrial intrinsic apoptotic pathway in HS-induced hyperpermeability and that the attenuation of this pathway may provide an alternative strategy in preserving vascular barrier integrity.

BAK; ischemia-reperfusion; protein transfection; cytochrome c; caspase-3

This article has been cited by other articles:

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