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 chondrocytes

2002 ◽  
Vol 30 (6) ◽  
pp. 886-889 ◽  
Author(s):  
S. J. Gilbert ◽  
V. C. Duance ◽  
D. J. Mason
Keyword(s):  
Protein Kinase ◽  
Tumour Necrosis ◽  
Cartilage Degradation ◽  
Initiation Factor ◽  
Tumour Necrosis Factor Α ◽  
Protein Kinase R ◽  
Initiation Factor 2 ◽  
Factor Α ◽  
Necrosis Factor

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.

scholarly journals The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration

2021 ◽  
Vol 13 ◽  
Author(s):  
Nicolás W. Martinez ◽  
Felipe E. Gómez ◽  
Soledad Matus
Keyword(s):  
Protein Kinase ◽  
Pathological Process ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Protein Kinase R ◽  
Eukaryotic Translation ◽  
Neurodegenerative Process ◽  
Age Related ◽  
Initiation Factor 2

There is a growing evidence describing a decline in adaptive homeostasis in aging-related diseases affecting the central nervous system (CNS), many of which are characterized by the appearance of non-native protein aggregates. One signaling pathway that allows cell adaptation is the integrated stress response (ISR), which senses stress stimuli through four kinases. ISR activation promotes translational arrest through the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) and the induction of a gene expression program to restore cellular homeostasis. However, depending on the stimulus, ISR can also induce cell death. One of the ISR sensors is the double-stranded RNA-dependent protein kinase [protein kinase R (PKR)], initially described as a viral infection sensor, and now a growing evidence supports a role for PKR on CNS physiology. PKR has been largely involved in the Alzheimer’s disease (AD) pathological process. Here, we reviewed the antecedents supporting the role of PKR on the efficiency of synaptic transmission and cognition. Then, we review PKR’s contribution to AD and discuss the possible participation of PKR as a player in the neurodegenerative process involved in aging-related pathologies affecting the CNS.

Risk factors for herpes zoster in rheumatoid arthritis patients: the role of tumour necrosis factor-α inhibitors

2015 ◽  
Vol 45 (3) ◽  
pp. 310-318 ◽  
Author(s):  
J. Segan ◽  
M. P. Staples ◽  
L. March ◽  
M. Lassere ◽  
E. F. Chakravarty ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Herpes Zoster ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Role of anti-tumour necrosis factor-α therapeutic agents in the emergence of infections

2006 ◽  
Vol 12 (12) ◽  
pp. 1151-1153 ◽  
Author(s):  
M.P. Moiton ◽  
C. Richez ◽  
C. Dumoulin ◽  
N. Mehsen ◽  
J. Dehais ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Therapeutic Agents ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor
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