Cross-talk between the calpain and caspase-3 proteolytic systems in the diaphragm during prolonged mechanical ventilation

• DOI: 10.1097/ccm.0b013e318246bb5d
• Publication Date: 2012-04-08T06:57:26Z
• Authors: W. Bradley Nelson; Ashley J. Smuder; Matthew B. Hudson; Erin E. Talbert; Scott K. Powers
• Keywords: Calpastatin

Diaphragmatic weakness, due to both atrophy and contractile dysfunction, is a well-documented response following prolonged mechanical ventilation. Evidence indicates that activation of the proteases calpain caspase-3 essential for ventilation-induced diaphragmatic weakness occur. We tested hypothesis regulatory cross-talk exists between in diaphragm during To test this prediction, we determined whether selective pharmacological inhibition would prevent conversely abate activation.Animal study.University Research Laboratory.Female Sprague-Dawley rats.Animals were randomly divided into control or one three 12-hr ventilation groups treated with/without protease inhibitor: 1) control, 2) ventilation, 3) with inhibitor, 4) inhibitor.Compared resulted accompanied by type I, IIa, IIx/IIb fibers. Independent either prevented atrophy. Pharmacological calpain. Furthermore, also caspase-9 caspase-12, along cleavage Bid tBid, all upstream signals activation. Lastly, degradation endogenous calpastatin.Collectively, these results indicate dependent on caspase-3. Importantly, findings provide first experimental evidence muscle prevents vice versa These support our calpain/caspase-3 whereby can promote active enhance activity