scholarly journals Inhibition of extracellular signal-regulated kinase 1 by adenovirus mediated small interfering RNA attenuates hepatic fibrosis in rats

Hepatology ◽  
2009 ◽  
Vol 50 (5) ◽  
pp. 1524-1536 ◽  
Author(s):  
Wei Zhong ◽  
Wei-Feng Shen ◽  
Bei-Fang Ning ◽  
Ping-Fang Hu ◽  
Yong Lin ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Small Interfering Rna ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Interfering Rna

scholarly journals ERK1c regulates Golgi fragmentation during mitosis

2006 ◽  
Vol 172 (6) ◽  
pp. 885-897 ◽  
Author(s):  
Yoav D. Shaul ◽  
Rony Seger
Keyword(s):  
Small Interfering Rna ◽  
Cell Cycle Regulation ◽  
Mitotic Progression ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Alternatively Spliced ◽  
Golgi Fragmentation ◽  
Cycle Regulation ◽  
Interfering Rna ◽  
Expression And Activity

Extracellular signal-regulated kinase 1c (ERK1c) is an alternatively spliced form of ERK1 that is regulated differently than other ERK isoforms. We studied the Golgi functions of ERK1c and found that it plays a role in MEK-induced mitotic Golgi fragmentation. Thus, in late G2 and mitosis of synchronized cells, the expression and activity of ERK1c was increased and it colocalized mainly with Golgi markers. Small interfering RNA of ERK1c significantly attenuated, whereas ERK1c overexpression facilitated, mitotic Golgi fragmentation. These effects were also reflected in mitotic progression, indicating that ERK1c is involved in cell cycle regulation via modulation of Golgi fragmentation. Although ERK1 was activated in mitosis as well, it could not replace ERK1c in regulating Golgi fragmentation. Therefore, MEKs regulate mitosis via all three ERK isoforms, where ERK1c acts specifically in the Golgi, whereas ERK1 and 2 regulate other mitosis-related processes. Thus, ERK1c extends the specificity of the Ras-MEK cascade by activating ERK1/2-independent processes.

scholarly journals Suppression of CB1 Cannabinoid Receptor by Lentivirus Mediated Small Interfering RNA Ameliorates Hepatic Fibrosis in Rats

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50850 ◽  
Author(s):  
Si-Wen Chen ◽  
Ben-Yan Wu ◽  
Shi-Ping Xu ◽  
Ke-Xing Fan ◽  
Li Yan ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Small Interfering Rna ◽  
Cannabinoid Receptor ◽  
Cb1 Cannabinoid Receptor ◽  
Interfering Rna

Acupuncture Combined with Curcumin Disrupts Platelet-Derived Growth Factor β Receptor/Extracellular Signal-Regulated Kinase Signalling and Stimulates Extracellular Matrix Degradation in Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats

2012 ◽  
Vol 30 (4) ◽  
pp. 324-330 ◽  
Author(s):  
Xiao-Ping Zhang ◽  
Feng Zhang ◽  
Zi-Li Zhang ◽  
Jin Ma ◽  
De-Song Kong ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Carbon Tetrachloride ◽  
Growth Factor ◽  
Hepatic Fibrosis ◽  
Combination Treatment ◽  
Acupuncture Treatment ◽  
Platelet Derived Growth Factor ◽  
Fibrotic Liver ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

Background Acupuncture treatment has been increasingly used to treat chronic liver diseases. We previously reported that acupuncture combined with curcumin, a natural antifibrotic compound, could remarkably attenuate liver fibrosis in chemically intoxicated rats, but the underlying molecular mechanisms are poorly understood. The present study was aimed at investigating the effects of acupuncture combined with curcumin on platelet-derived growth factor (PDGF) signalling and extracellular matrix (ECM) regulation in the fibrotic liver. Methods A total of 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination treatment groups. During the establishment of fibrosis using carbon tetrachloride (CCl4), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, serum PDGF levels were measured. Protein and mRNA expression of key effectors in PDGF pathway and fibrinolysis in the liver was determined. Results Acupuncture combined with curcumin potently reduced serum PDGF levels and selectively disrupted the PDGF-βR/extracellular signal-regulated kinase (ERK) cascade. Combination treatment also significantly repressed expression of connective tissue growth factor and upregulated expression of matrix metalloproteinase-9, promoting fibrinolysis in the fibrotic liver. Conclusions The beneficial effects of acupuncture and its combination with curcumin could be attributed to the disruption of PDGF-βR/ERK pathway and stimulated ECM degradation in the fibrotic liver. Acupuncture treatment significantly enhanced curcumin effects at the molecular level. These findings may provide molecular insights into the potential of acupuncture combined with curcumin for prevention of hepatic fibrosis.

scholarly journals Extracellular Signal-Regulated Kinase Activation by Neisseria gonorrhoeae Downregulates Epithelial Cell Proapoptotic Proteins Bad and Bim

2008 ◽  
Vol 76 (6) ◽  
pp. 2715-2721 ◽  
Author(s):  
Heather L. Howie ◽  
Shelly L. Shiflett ◽  
Magdalene So
Keyword(s):  
Epithelial Cell ◽  
Neisseria Gonorrhoeae ◽  
Kinase Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Type Iv ◽  
Extracellular Signal ◽  
Domain 3 ◽  
Induced Apoptosis ◽  
Dependent Modification ◽  
Interfering Rna

ABSTRACT Neisseria gonorrhoeae expressing type IV pili (Tfp) activates extracellular signal-regulated kinase (ERK) and induces a cytoprotective state in the epithelial cell in a manner that is enhanced by pilT. As the ERK signaling pathway is well-known for its role in cytoprotection and cell survival, we tested the hypothesis that ERK is involved in producing this cytoprotective effect. Inhibiting ERK activation prior to infection attenuated the ability of these bacteria to induce cytoprotection. Activated ERK specifically targeted two proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins, Bim and Bad, for downregulation at the protein level. Bim downregulation occurred through the proteasome. ERK, in addition, inactivated Bad by triggering its phosphorylation at Ser112. Finally, reducing the level of either Bad or Bim alone by small interfering RNA was sufficient to protect uninfected cells from staurosporine-induced apoptosis. We conclude that Tfp-induced cytoprotection is due in part to ERK-dependent modification and/or downregulation of proapoptotic proteins Bad and Bim.

scholarly journals Effect of SOCS1 silencing on proliferation and apoptosis of melanoma cells: An in vivo and in vitro study

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769431
Author(s):  
Sheng-Jia Yu ◽  
Zi-Wen Long
Keyword(s):  
Messenger Rna ◽  
Small Interfering Rna ◽  
Melanoma Cells ◽  
Janus Kinase ◽  
Extracellular Signal ◽  
Proliferation And Apoptosis ◽  
Protein Expressions ◽  
Interfering Rna

This study aimed to investigate the effect of SOCS1 silencing on the proliferation and apoptosis of melanoma cells by in vivo and in vitro studies. Immunohistochemical staining was used to detect SOCS1 expression in melanoma tissues and pigmented nevi. Quantitative real-time polymerase chain reaction and western blotting were applied to detect the messenger RNA and protein expressions of SOCS1 in primary human melanocytes and malignant melanoma cell lines (A375, SK-MEL-5, M14, and MV3). Melanoma cells were assigned into mock, negative small interfering RNA, and SOCS1-small interfering RNA groups. The proliferation, cell cycle and apoptosis, and messenger RNA expression of SOCS1 in MV3 and A375 cells were detected using MTT assay, flow cytometry, and quantitative real-time polymerase chain reaction, respectively. The expressions of SOCS1 protein, extracellular signal–regulated kinase, and janus kinase signal transduction and activators of transcription signaling pathways–related proteins were detected using western blotting. After the establishment of subcutaneous xenograft tumor models in nude mice, the latent period, size, volume and growth speed of xenograft tumors in the mock, negative small interfering RNA, and SOCS1-small interfering RNA groups were examined and compared. The results indicated that positive expression rate of SOCS1 was higher in malignant melanoma tissues than in pigmented nevi. MV3 cells had the highest messenger RNA and protein expressions of SOCS1, followed by A357 cells. Compared with the mock and negative small interfering RNA groups, SOCS1-small interfering RNA group showed lower cell viability, elevated cell apoptosis, more cells in G0/G1 phase and less cells in S and G2/M phases, and decreased messenger RNA and protein expressions of SOCS1, p-ERK1/2, p-JAK2, p-STAT1, and p-STAT3. Compared with the mock and negative small interfering RNA groups, the SOCS1-small interfering RNA group showed longer latent period of tumor, smaller tumor size and volume, and smoother tumor growth curve. To conclude, SOCS1 silencing can inhibit proliferation and induce apoptosis of MV3 and A357 melanoma cells in vivo and in vitro by inhibiting extracellular signal–regulated kinase and janus kinase signal transduction and activators of transcription signaling pathways.

scholarly journals The S1P2 Receptor Negatively Regulates Platelet-Derived Growth Factor-Induced Motility and Proliferation

2005 ◽  
Vol 25 (10) ◽  
pp. 4237-4249 ◽  
Author(s):  
Sravan K. Goparaju ◽  
Puneet S. Jolly ◽  
Kenneth R. Watterson ◽  
Meryem Bektas ◽  
Sergio Alvarez ◽  
...  
Keyword(s):  
Growth Factor ◽  
Growth Factor Receptor ◽  
Negative Regulator ◽  
Platelet Derived Growth Factor ◽  
Embryonic Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Sphingosine 1 Phosphate ◽  
Interfering Rna ◽  
G Protein Coupled

ABSTRACT Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is the ligand for five specific G protein-coupled receptors, named S1P1 to S1P5. In this study, we found that cross-communication between platelet-derived growth factor receptor and S1P2 serves as a negative damper of PDGF functions. Deletion of the S1P2 receptor dramatically increased migration of mouse embryonic fibroblasts toward S1P, serum, and PDGF but not fibronectin. This enhanced migration was dependent on expression of S1P1 and sphingosine kinase 1 (SphK1), the enzyme that produces S1P, as revealed by downregulation of their expression with antisense RNA and small interfering RNA, respectively. Although S1P2 deletion had no significant effect on tyrosine phosphorylation of the PDGF receptors or activation of extracellular signal-regulated kinase 1/2 or Akt induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and markedly enhanced Rac activation. Surprisingly, S1P2-null cells not only exhibited enhanced proliferation but also markedly increased SphK1 expression and activity. Conversely, reintroduction of S1P2 reduced DNA synthesis and expression of SphK1. Thus, S1P2 serves as a negative regulator of PDGF-induced migration and proliferation as well as SphK1 expression. Our results suggest that a complex interplay between PDGFR and S1P receptors determines their functions.

β-Arrestin-recruited phosphodiesterase-4 desensitizes the AKAP79/PKA-mediated switching of β2-adrenoceptor signalling to activation of ERK

2005 ◽  
Vol 33 (6) ◽  
pp. 1333-1336 ◽  
Author(s):  
M.D. Houslay ◽  
G.S. Baillie
Keyword(s):  
Functional Role ◽  
Dominant Negative ◽  
Functional Importance ◽  
Extracellular Signal Regulated Kinase ◽  
Phosphodiesterase 4 ◽  
Camp Synthesis ◽  
Extracellular Signal ◽  
Anchoring Protein ◽  
Interfering Rna

Using combined dominant-negative and siRNA (small interfering RNA)-mediated knockdown strategies, the functional importance of specific PDE4 (phosphodiesterase-4) isoforms in modifying signalling through the β2-AR (β2-adrenoceptor) has been uncovered. The PDE4D5 isoform preferentially interacts with the signalling scaffold protein β-arrestin and is thereby recruited to the β2-AR upon agonist challenge. Delivery of an active PDE to the site of cAMP synthesis at the plasma membrane specifically attenuates the activity of a pool of PKA (protein kinase A) that is tethered to the β2-AR via AKAP79 (A-kinase anchoring protein 79). The specific functional role of this anchored PKA is to phosphorylate the β2-AR and allow it to switch its coupling with Gi and thereby activation of ERK (extracellular-signal-regulated kinase). Our studies uncover a novel facet of the regulation of β2-AR signalling by showing that β-arrestin-recruited PDE4 provides the means of desensitizing the agonist-dependent coupling of β2-AR with Gi and its consequential activation of ERK.

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