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10:23
Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Calpain activation contributes to endotoxin-induced diaphragmatic dysfunction
Gerald S Supinski1, Leigh Ann Callahan
1Department of Medicine, 740 South Limestone, University of Kentucky, Lexington, KY 40536-0284, USA. gsupi2@email.uky.edu
American Journal of Respiratory Cell and Molecular Biology
|March 31, 2009
Summary
Infection activates calpain in the diaphragm, weakening respiratory muscles. Calpain inhibitors can prevent this muscle weakness, offering potential treatment for infected patients.
Area of Science:
- Biomedical Science
- Muscle Physiology
- Sepsis Research
Background:
- Calpain activation is observed in skeletal muscle during infection.
- The impact of calpain inhibition on muscle function during infection remains unclear.
Purpose of the Study:
- To investigate if calpain inhibition improves diaphragm muscle function during infection.
- To determine if infection induces diaphragm calpain activation and subsequent cytoskeletal protein cleavage.
Main Methods:
- Mice were administered endotoxin and/or a calpain inhibitor peptide III.
- Diaphragm calpain activity, protein levels, talin degradation, and force-frequency relationships were assessed.
- A fluorogenic assay was used to measure calpain activity.
Main Results:
- Endotoxin significantly increased diaphragm calpain activity, active calpain levels, and talin degradation.
- Endotoxin administration led to a significant reduction in diaphragm force.
- Calpain inhibitor III administration prevented these endotoxin-induced effects and attenuated diaphragm weakness.
Conclusions:
- Sepsis models induce significant diaphragm calpain activation and protein cleavage.
- Calpain inhibition effectively mitigates infection-induced diaphragm dysfunction.
- Calpain inhibitors show promise for improving respiratory muscle function in infected individuals.
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