Caspase-mediated protein kinase C-δ cleavage is necessary for apoptosis of vascular smooth muscle cells

Kaori Kato, Dai Yamanouchi, Karla Esbona, Kentaro Kamiya, Fan Zhang, K. Craig Kent, Bo Liu

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)

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-δ (PKC-δ) plays a critical role in SMC apoptosis. In this study, we tested the importance of PKC-δ 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-δ 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-δ, we were able to prevent the cleavage of PKC-δ, as well as apoptosis. Inhibition of PKC-δ with rottlerin or small-interfering RNA diminished caspase-3 cleavage, caspase-3 activity, cleavage of poly (ADPribose) polymerase, cleavage of PKC-δ, and DNA fragmentation, confirming the previously reported role of PKC-δ in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished caspase-3 activity, cleavage of PKC-δ, and DNA fragmentation without affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together, our data suggest that caspase-3-mediated PKC-δ cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-δ acts both upstream and downstream of caspase-3.

Original languageEnglish
Pages (from-to)H2253-H2261
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number6
DOIs
Publication statusPublished - 12-2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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