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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Apoptosis, DNA Fragmentation, I-kappa B Kinase, Kupffer Cells, Male, Molecular Chaperones, Rats, Rats, Sprague-Dawley, Sepsis, Translocation, Genetic, Up-Regulation.
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Does protein kinase C-zeta ( PKC-zeta ) regulate Kupffer cell apoptosis during experimental sepsis? Context: Kupffer cells play an important role in sepsis-mediated liver injury. We tested the hypothesis that PKC-zeta plays a critical role in Kupffer cell apoptosis during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP); 12 h later, livers were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation. Kupffer cells from control rats were infected with AdPKC-zeta DN to inhibit PKC-zeta, or transfected with pCMVPKC-zeta to overexpress PKC-zeta, and then treated with lipopolysaccharide (LPS). Cellular extracts were assayed for PKC-zeta, IKKalpha, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation. During sepsis, PKC-zeta localized in cells positive for the macrophage marker (F4/80). CLP 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). AdPKC-zeta DN attenuated the LPS-induced upregulation of PKC-zeta activity, IKKbeta, IKKgamma, NF-kappaB, Fas/FasL, Caspase-3, and DNA fragmentation in Kupffer cells (all p<0.001), whereas overexpression of PKC-zeta augmented LPS-induced upregulation of IKKbeta, IKKgamma, NF-kappaB, Caspase-3, and DNA fragmentation (p<0.001).
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PKC-zeta plays an important role in sepsis-induced apoptosis of Kupffer cells via activation of NF-kappaB and Fas/FasL. Manipulating the response of Kupffer cells to cellular stress may have important therapeutic implications. Final Decision: yes