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Published on: September 27, 2016
Enhanced Hsp70 expression protects against acute lung injury by modulating apoptotic pathways
Gabriella Aschkenasy1, Zohar Bromberg, Nichelle Raj
1Department of Anesthesiology and Critical Care Medicine and the Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University School of Medicine, Jerusalem, Israel.
Plos One
|December 2, 2011
Summary
Adenovirus-mediated heat shock protein 70 (AdHSP) therapy reduces apoptosis in sepsis-induced lung injury by disrupting caspase complexes. This protects alveolar cells and may aid recovery from acute respiratory distress syndrome (ARDS).
Area of Science:
- Cellular Biology
- Pathology
- Molecular Medicine
Background:
- Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition with high mortality.
- Apoptosis, or programmed cell death, is a critical factor in ARDS development.
- Previous studies indicated that heat shock protein 70 (Hsp70) confers protection against sepsis-induced lung injury.
Purpose of the Study:
- To investigate whether AdHSP can attenuate apoptosis in sepsis-induced lung injury.
- To elucidate the molecular mechanisms by which AdHSP affects apoptotic pathways in lung injury.
Main Methods:
- Sepsis was induced in rats using cecal ligation and double puncture (2CLP).
- Adenoviral vectors (AdHSP or AdGFP) were administered intratracheally.
- Lung tissues and MLE-12 cells were analyzed using TUNEL staining, immunohistochemistry, immunoblotting, co-immunoprecipitation, gel filtration, and caspase-3 activity assays.
Main Results:
- AdHSP treatment significantly reduced alveolar cell apoptosis, as evidenced by TUNEL assays and decreased caspase-3 abundance.
- In septic rat lungs, AdHSP disrupted cytoplasmic complexes containing caspases 3, 8, and 9.
- In vitro studies showed AdHSP interfered with caspase activation in TNFα-stimulated MLE-12 cells.
Conclusions:
- Hsp70, delivered via AdHSP, inhibits apoptotic cellular pathways by interacting with caspases.
- Disruption of caspase complexes by Hsp70 leads to reduced nuclear caspase-3 activity.
- AdHSP-mediated prevention of apoptosis may preserve lung function and improve recovery in ARDS.
