کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4309019 | 1289298 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Protein kinase C-zeta mediates apoptosis of mouse Kupffer cells via ERK-1/2: A novel mechanism Protein kinase C-zeta mediates apoptosis of mouse Kupffer cells via ERK-1/2: A novel mechanism](/preview/png/4309019.png)
BackgroundWe have demonstrated that activated Kupffer cells undergo accelerated apoptosis via Toll-like receptor (TLR)-4 and protein kinase C (PKC)-ζ–dependent nuclear factor (NF)-κB activation. Because PKC-ζ plays a pivotal role in cell signaling, we sought to determine the signaling pathway of PKC-ζ in Kupffer cell apoptosis.MethodsMouse Kupffer cell line (MKCL3-2) were transfected with PKC-ζ small interfering RNA (siRNA) and then treated with elastase alone or elastase along with the extracellular signal-regulated kinase (ERK) inhibitor U0126. Cell extracts were assayed for PKC-ζ (protein and activity), TLR-4, NF-κB nuclear translocation, phosphorylated ERK-1/2, activated caspase-3, and DNA fragmentation. All n ≥3; data are expressed as mean values ± standard deviations; means were compared using the t test; P < .05 was considered significant.ResultsElastase upregulated TLR-4, PKC-ζ, NF-κB, ERK-1/2, caspase-3, and DNA fragmentation (all P < .01 versus control). Transfection with PKC-ζ siRNA attenuated the elastase-induced upregulation of PKC-ζ activity, NF-κB, ERK-1/2, caspase-3, and DNA fragmentation (all P < .01 versus control). The interaction of PKC-ζ with ERK-1/2 was increased by elastase and was attenuated by PKC-ζ siRNA as confirmed by co-immunoprecipitation and immunofluorescent staining.ConclusionActivation of Kupffer cells upregulates PKC-ζ activity, increases apoptosis, and induces nuclear translocation of NF-κB via ERK-1/2–dependent pathways. Inhibiting the activity of PKC-ζ significantly attenuates Kupffer cell apoptosis, NF-κB, and ERK-1/2 activation. The interaction of PKC-ζ and ERK-1/2 warrants further investigation.
Journal: Surgery - Volume 149, Issue 1, January 2011, Pages 135–142