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Caspase‐3 is activated by intrinsic apoptotic pathways during mechanical ventilation
Author(s) -
Nelson W. Bradley,
Smuder Ashley J.,
Hudson Mathew B.,
Talbert Erin E.,
Powers Scott K.
Publication year - 2011
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.25.1_supplement.lb590
Subject(s) - caspase , caspase 9 , caspase 12 , caspase 3 , caspase 8 , diaphragm (acoustics) , diaphragmatic breathing , apoptosis , microbiology and biotechnology , mechanical ventilation , chemistry , medicine , biology , biochemistry , pathology , programmed cell death , physics , alternative medicine , acoustics , loudspeaker
Rationale Diaphragmatic weakness is a well‐documented response to prolonged mechanical ventilation (MV). Several key proteases are activated during prolonged MV. Specifically, caspase‐3 has been shown to be required for diaphragmatic weakness. However, the mechanisms by which caspase‐3 is activated is unknown. We tested the hypothesis that during MV, caspase‐3 is activated by an intrinsic pathway. Methods Female Sprague‐Dawley rats (3 months old) were divided into two groups: 1) control and 2) animals that were mechanically ventilated for 12 hrs. Results Compared to control, MV resulted in an increase in the caspase‐3 specific cleavage product of alpha‐II spectrin and increased caspase‐3 activity in the diaphragm. Likewise, after MV, both caspase‐9 and caspase‐12 activities in the diaphragm were significantly higher than control. In contrast, there was no increase in diaphragmatic caspase‐8 activity after MV. Conclusion These results confirm our hypothesis that during prolonged MV, diaphragmatic caspase‐3 is activated by both mitochondrial (caspase‐9) and sarcoplasmic reticulum (caspase‐12) mediated pathways rather than the external death ligand (caspase‐8) pathway. Supported by the NIH RO1 HL087839 awarded to SKP.