scholarly journals Regionally selective activation and differential regulation of ERK, JNK and p38 MAP kinase signalling pathway by protein kinase C in mood modulation

2011 ◽  
Vol 15 (06) ◽  
pp. 781-793 ◽  
Author(s):  
Nicoletta Galeotti ◽  
Carla Ghelardini
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Map Kinase ◽  
Differential Regulation ◽  
P38 Map Kinase ◽  
Signalling Pathway ◽  
Selective Activation ◽  
Kinase C

scholarly journals The Streptococcal Exotoxin Streptolysin O Activates Mast Cells To Produce Tumor Necrosis Factor Alpha by p38 Mitogen-Activated Protein Kinase- and Protein Kinase C-Dependent Pathways

2003 ◽  
Vol 71 (11) ◽  
pp. 6171-6177 ◽  
Author(s):  
Michael Stassen ◽  
Christian Müller ◽  
Christoph Richter ◽  
Christine Neudörfl ◽  
Lothar Hültner ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Mast Cells ◽  
Protein Kinase ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Necrosis Factor Alpha ◽  
Kinase C ◽  
Streptolysin O ◽  
Tnf Α ◽  
Mitogen Activated Protein

ABSTRACT Streptolysin O (SLO), a major virulence factor of pyogenic streptococci, binds to cholesterol in the membranes of eukaryotic cells and oligomerizes to form large transmembrane pores. While high toxin doses are rapidly cytocidal, low doses are tolerated because a limited number of lesions can be resealed. Here, we report that at sublethal doses, SLO activates primary murine bone marrow-derived mast cells to degranulate and to rapidly induce or enhance the production of several cytokine mRNAs, including tumor necrosis factor alpha (TNF-α). Mast cell-derived TNF-α plays an important protective role in murine models of acute inflammation, and the production of this cytokine was analyzed in more detail. Release of biologically active TNF-α peaked ∼4 h after stimulation with SLO. Production of TNF-α was blunted upon depletion of protein kinase C by pretreatment of the cells with phorbol-12 myristate-13 acetate. Transient permeabilization of mast cells with SLO also led to the activation of the stress-activated protein kinases p38 mitogen-activated protein (MAP) kinase and c-jun N-terminal kinase (JNK), and inhibition of p38 MAP kinase markedly reduced production of TNF-α. In contrast, secretion of preformed granule constituents triggered by membrane permeabilization was not dependent on p38 MAP kinase or on protein kinase C. Thus, transcriptional activation of mast cells following transient permeabilization might contribute to host defense against infections via the beneficial effects of TNF-α. However, hyperstimulation of mast cells might also lead to overproduction of TNF-α, which would then promote the development of toxic streptococcal syndromes.

scholarly journals Protein Kinase C-δ Regulates Thrombin-Induced ICAM-1 Gene Expression in Endothelial Cells via Activation of p38 Mitogen-Activated Protein Kinase

2001 ◽  
Vol 21 (16) ◽  
pp. 5554-5565 ◽  
Author(s):  
Arshad Rahman ◽  
Khandaker N. Anwar ◽  
Shahab Uddin ◽  
Ning Xu ◽  
Richard D. Ye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Map Kinase ◽  
Critical Role ◽  
P38 Map Kinase ◽  
Intercellular Adhesion Molecule ◽  
Kinase C ◽  
Mitogen Activated Protein

ABSTRACT The procoagulant thrombin promotes the adhesion of polymorphonuclear leukocytes to endothelial cells by a mechanism involving expression of intercellular adhesion molecule 1 (ICAM-1) via an NF-κB-dependent pathway. We now provide evidence that protein kinase C-δ (PKC-δ) and the p38 mitogen-activated protein (MAP) kinase pathway play a critical role in the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells. We observed the phosphorylation of PKC-δ and p38 MAP kinase within 1 min after thrombin challenge of human umbilical vein endothelial cells. Pretreatment of these cells with the PKC-δ inhibitor rottlerin prevented the thrombin-induced phosphorylation of p38 MAP kinase, suggesting that p38 MAP kinase signals downstream of PKC-δ. Inhibition of PKC-δ or p38 MAP kinase by pharmacological and genetic approaches markedly decreased the thrombin-induced NF-κB activity and resultant ICAM-1 expression. The effects of PKC-δ inhibition were secondary to inhibition of IKKβ activation and of subsequent NF-κB binding to the ICAM-1 promoter. The effects of p38 MAP kinase inhibition occurred downstream of IκBα degradation without affecting the DNA binding function of nuclear NF-κB. Thus, PKC-δ signals thrombin-induced ICAM-1 gene transcription by a dual mechanism involving activation of IKKβ, which mediates NF-κB binding to the ICAM-1 promoter, and p38 MAP kinase, which enhances transactivation potential of the bound NF-κB p65 (RelA).

scholarly journals Involvement of stress-activated protein kinase/c-Jun N-terminal kinase in endothelin-1-induced heat shock protein 27 in osteoblasts

2003 ◽  
pp. 239-245 ◽  
Author(s):  
H Tokuda ◽  
M Niwa ◽  
H Ito ◽  
Y Oiso ◽  
K Kato ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Map Kinase ◽  
Blot Analysis ◽  
Heat Shock Protein 27 ◽  
P38 Map Kinase ◽  
Endothelin 1 ◽  
Kinase C

OBJECTIVE: We have reported that endothelin-1 (ET-1) activates p38 mitogen-activated protein (MAP) kinase through protein kinase C in osteoblast-like MC3T3-E1 cells, and that p38 MAP kinase plays a role in the ET-1-induced heat shock protein 27 (HSP27). Recently, we found that stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is activated by ET-1 in these cells. In the present study, we have investigated the involvement of SAPK/JNK in ET-1-induced HSP27 in MC3T3-E1 cells. METHODS: The concentration of HSP27 in soluble extracts of the cells, the expression of mRNA for HSP27, and the phosphorylation of SAPK/JNK were determined by an enzyme immunoassay, Northern blot analysis, and Western blot analysis respectively. RESULTS: SP600125, a specific inhibitor of SAPK/JNK, markedly reduced ET-1-stimulated HSP27 accumulation. The inhibitory effect of SP600125 was dose dependent in the range between 1 and 50 microM. SP600125 reduced the ET-1-increased level of HSP27 mRNA. Calphostin C and Go 6976, inhibitors of protein kinase C, reduced the ET-1-induced phosphorylation of SAPK/JNK. 12-O-Tetradecanoylphorbol-13-acetate, a direct activator of protein kinase C, induced SAPK/JNK phosphorylation, which was suppressed by SP600125. A combination of SP600125 and p38 MAP kinase inhibitor such as SB203580 and PD169316 additively reduced the ET-1-stimulated accumulation of HSP27. CONCLUSIONS: These results strongly suggest that JNK plays a part in ET-1-induced HSP27 in addition to p38 MAP kinase in osteoblasts.

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