Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.5 (
cathepsin D
)
4,130
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated
cathepsin D
occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of
cathepsin D
during pneumococcal infection blocked macrophage apoptosis. As a result of
cathepsin D
activation, Mcl-1 interacted with its ubiquitin ligase
Mule
and expression declined. Inhibition of
cathepsin D
had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a
cathepsin D
(-/-) hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a
cathepsin D
-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function.
...
PMID:A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci. 2129 30
