Caspase-mediated protein kinase C-delta cleavage is necessary for apoptosis of vascular smooth muscle cells.
Am J Physiol Heart Circ Physiol
; 297(6): H2253-61, 2009 Dec.
Article
in En
| MEDLINE
| ID: mdl-19837952
ABSTRACT
Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling and various vascular diseases. We have previously shown that protein kinase C-delta (PKC-delta) plays a critical role in SMC apoptosis. In this study, we tested the importance of PKC-delta proteolytic cleavage and tyrosine phosphorylation within the apoptosis pathway. Using hydrogen peroxide as a paradigm for oxidative stress, we showed that proteolytic cleavage of PKC-delta occurred in SMCs that underwent apoptosis, while tyrosine phosphorylation was detected only in necrotic cells. Furthermore, using a peptide (z-DIPD-fmk) that mimics the caspase-3 binding motif within the linker region of PKC-delta, we were able to prevent the cleavage of PKC-delta, as well as apoptosis. Inhibition of PKC-delta with rottlerin or small-interfering RNA diminished caspase-3 cleavage, caspase-3 activity, cleavage of poly (ADP-ribose) polymerase, cleavage of PKC-delta, and DNA fragmentation, confirming the previously reported role of PKC-delta in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished caspase-3 activity, cleavage of PKC-delta, and DNA fragmentation without affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together, our data suggest that caspase-3-mediated PKC-delta cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-delta acts both upstream and downstream of caspase-3.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Processing, Post-Translational
/
Apoptosis
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Myocytes, Smooth Muscle
/
Protein Kinase C-delta
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Caspase 3
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Muscle, Smooth, Vascular
Limits:
Animals
Language:
En
Journal:
Am J Physiol Heart Circ Physiol
Journal subject:
CARDIOLOGIA
/
FISIOLOGIA
Year:
2009
Document type:
Article
Affiliation country:
United States