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Tumour necrosis factor α up-regulates protein kinase R (PKR)-activating protein (PACT) and increases phosphorylation of PKR and eukaryotic initiation factor 2-α in articular chondrocyte

Gilbert, Sophie Jane, Duance, Victor Colin ORCID: https://orcid.org/0000-0002-7555-2016 and Mason, Deborah Jane ORCID: https://orcid.org/0000-0002-8666-6094 2002. Tumour necrosis factor α up-regulates protein kinase R (PKR)-activating protein (PACT) and increases phosphorylation of PKR and eukaryotic initiation factor 2-α in articular chondrocyte. Biochemical Society Transactions 30 , pp. 886-889. 10.1042/bst0300886

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Abstract

Our previous analysis of the genes regulated in cartilage at the onset of spontaneous osteoarthritis in the guinea pig knee revealed up-regulation of the gene for protein kinase R (PKR)-activating protein (PACT), which encodes the cellular activator of the protein kinase, PKR. PACT and PKR are upstream components of a number of signal transduction and gene transcription pathways used by pro-inflammatory cytokines. We have investigated the role of PACT and PKR in articular cartilage degradation using cytokine treatment of bovine primary chondrocytes and cartilage explants. Tumour necrosis factor α increased expression of PACT protein after 3 h of treatment. Furthermore, increased phosphorylation of PKR and eukaryotic initiation factor 2-α was observed. The known role of PKR in cytokine-induced signalling pathways, together with our data showing cytokine regulation of PACT and PKR in chondrocytes, reveals a novel mechanism of cartilage degradation that may be important in the pathogenesis of arthritic diseases.

Item Type: Article
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Publisher: Portland Press
ISSN: 0300-5127
Last Modified: 27 Oct 2022 10:12
URI: https://orca.cardiff.ac.uk/id/eprint/69295

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