Protein kinase C-zeta is critical in pancreatitis-induced apoptosis of Kupffer cells.

Published

Journal Article

Protein kinase C-zeta (PKC-zeta) regulates cell death via NF-kappaB; therefore, we tested the hypothesis that PKC-zeta plays a critical role in pancreatitis-induced Kupffer cell apoptosis. Acute pancreatitis was induced in rats by cerulein injection 24 h later, livers were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, and apoptosis was assessed with Caspase-3 and DNA fragmentation. Kupffer cells from unoperated rats were infected with a PKC-zeta domain-negative adenovirus (AdPKCzeta-DN) to inhibit PKC-zeta, or transfected with pCMVPKC-zeta to overexpress PKC-zeta, and then stimulated with pancreatic elastase; cellular extracts were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation. Cerulein-induced pancreatitis upregulated PKC-zeta protein and activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3 and increased DNA fragmentation in rat livers (all p < 0.001 vs control). AdPKCzeta-DN abolished elastase-induced upregulation of PKC-zeta activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3 and DNA fragmentation (all p < 0.001 vs infection control), whereas overexpression of PKC-zeta augmented elastase-induced upregulation of IKKbeta, IKKgamma, Fas/FasL, Caspase-3 and DNA fragmentation (p < 0.001 vs control). PKC-zeta plays a critical role in pancreatitis-induced Kupffer cell apoptosis via NF-kappaB and Fas/FasL. The ability of Kupffer cells to autoregulate their stress response by upregulating their death receptor/ligand and key proapoptotic cell signaling systems warrants further investigation.

Full Text

Duke Authors

Cited Authors

  • Peng, Y; Sigua, CA; Gallagher, SF; Murr, MM

Published Date

  • October 2007

Published In

Volume / Issue

  • 11 / 10

Start / End Page

  • 1253 - 1261

PubMed ID

  • 17653813

Pubmed Central ID

  • 17653813

Electronic International Standard Serial Number (EISSN)

  • 1873-4626

International Standard Serial Number (ISSN)

  • 1091-255X

Digital Object Identifier (DOI)

  • 10.1007/s11605-007-0193-0

Language

  • eng