scholarly journals [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sung Ok Kim ◽  
Mi Ryeo Kim
Keyword(s):  
Signal Transduction ◽  
Nuclear Translocation ◽  
Signal Transduction Pathway ◽  
Cancer Cell Line ◽  
Duct Cell ◽  
Cell Junctions ◽  
Human Pancreas ◽  
Erk Pathway ◽  
Protein Levels ◽  
Extracellular Signal

To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ) molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP) activities; transepithelial electrical resistance (TER) and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO-) 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK) pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

scholarly journals The β-Arrestin-Like Protein Rim8 Is Hyperphosphorylated and Complexes with Rim21 and Rim101 To Promote Adaptation to Neutral-Alkaline pH

2012 ◽  
Vol 11 (5) ◽  
pp. 683-693 ◽  
Author(s):  
Jonathan Gomez-Raja ◽  
Dana A. Davis
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
G Protein ◽  
Signal Transduction Pathway ◽  
Multivesicular Bodies ◽  
Ph Sensing ◽  
Content Type ◽  
Protein Levels ◽  
G Protein Coupled

ABSTRACTβ-Arrestin proteins are critical for G-protein-coupled receptor desensitization and turnover. However, β-arrestins have recently been shown to play direct roles in nonheterotrimeric G-protein signal transduction. TheCandida albicansβ-arrestin-like protein Rim8 is required for activation of the Rim101 pH-sensing pathway and for pathogenesis. We have found thatC. albicansRim8 is posttranslationally modified by phosphorylation and specific phosphorylation states are associated with activation of the pH-sensing pathway. Rim8 associated with both the receptor Rim21 and the transcription factor Rim101, suggesting that Rim8 bridges the signaling and activation steps of the pathway. Finally, upon activation of the Rim101 transcription factor,C. albicansRim8 was transcriptionally repressed and Rim8 protein levels were rapidly reduced. Our studies suggest that Rim8 is taken up into multivesicular bodies and degraded within the vacuole. In total, our results reveal a novel mechanism for tightly regulating the activity of a signal transduction pathway. Although the role of β-arrestin proteins in mammalian signal transduction pathways has been demonstrated, relatively little is known about how β-arrestins contribute to signal transduction. Our analyses provide some insights into potential roles.

scholarly journals Radiotherapy and inhibition of the EGF family as treatment strategies for prostate cancer: combining theragnostics with theragates

2011 ◽  
Vol 5 (2) ◽  
pp. 119 ◽  
Author(s):  
Wolfgang Lilleby ◽  
Flavio Solca ◽  
Kathrine Røe
Keyword(s):  
Prostate Cancer ◽  
Signal Transduction ◽  
Solid Tumors ◽  
Kinase Inhibitors ◽  
Nuclear Translocation ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Signal Transduction Pathway ◽  
Protein Kinase Inhibitors ◽  
Treatment Modalities

Prostate cancer is one of the most common solid tumors affecting men. Localized stages can be cured, however, once disseminated to distant organs the median survival drops below 12 months. The challenge for the future consists of unifying gained insights of cellular signal dysfunctioning (‘‘theragates’’) with the knowledge of disease detection (‘‘theragnostics’’) in personalized therapy. In solid malignancies, multiple signal transduction molecules are often deregulated simultaneously, within the same tumor. A multi-targeted approach may possibly improve efficacy, but will also increase toxicity, thus, potentially limiting the use of various combinations. On the other hand, well-established treatment modalities in prostate cancer, such as radiotherapy with its known efficacy and limited toxicity, may be an attractive combination partner for protein kinase inhibitors. Deregulation of the epidermal growth factor receptor (EGFR) signal transduction pathway is observed in a variety of solid tumors, including prostate cancer. Furthermore, one important DNA repair mechanism is dependent on EGFR nuclear translocation, thus, providing a rationale for combining radiotherapy with EGFR inhibitors. This article reviews current knowledge regarding this combination paradigm, revealing an intriguing therapy option to be explored for patients with advanced prostate cancer.

scholarly journals Evidence That Dynamin-2 Functions as a Signal-Transducing Gtpase

2000 ◽  
Vol 150 (1) ◽  
pp. 145-154 ◽  
Author(s):  
Kenneth N. Fish ◽  
Sandra L. Schmid ◽  
Hanna Damke
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathway ◽  
Fold Increase ◽  
Protein Levels ◽  
Rich Domain ◽  
Dividing Cells ◽  
Additional Support ◽  
Transcription Factor P53 ◽  
New Evidence ◽  
Dynamin 2

The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is well established. Here, we present new evidence that the ubiquitously expressed isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A ≤5-fold increase of dyn2 relative to endogenous levels activates the transcription factor p53 and induces apoptosis, as demonstrated by reduced cell proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective in GTP binding does not trigger apoptosis, indicating that increased levels of dyn2·GTP, rather than protein levels per se, are required to transduce signals that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine-rich domain (PRD), which interacts with many SH3 domain-containing partners implicated in both endocytosis and signal transduction, triggers apoptosis even more potently than the wild-type. This observation provides additional support for the importance of the NH2-terminal GTPase domain for the apoptotic phenotype. All described effects are dyn2-specific because >200-fold overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our data suggest that dyn2 can act as a signal transducing GTPase affecting transcriptional regulation.

CK2 Is Acting Upstream of MEK3/6 as a Part of the Signal Control of ERK1/2 and p38 MAPK during Keratinocytes Autocrine Differentiation

2011 ◽  
Vol 66 (1-2) ◽  
pp. 83-86 ◽  
Author(s):  
Antonia R. Isaeva ◽  
Vanio I. Mitev
Keyword(s):  
Signal Transduction ◽  
P38 Mapk ◽  
Mammalian Cells ◽  
Protein Kinase Ck2 ◽  
Cell Signalling ◽  
Signal Transduction Pathway ◽  
Signal Control ◽  
Transduction Pathway ◽  
Protein Levels ◽  
Kinase Ck2

Protein kinase CK2 (formerly termed “casein kinase II”) is a ubiquitously in mammalian cells distributed Ser/Thr kinase, with global role in cell regulation. Although, the involvement of CK2 in cell signalling is vast-investigated, virtually nothing is known about its contribution to signal control of keratinocytes differentiation. Here we show that, in autocrine differentiating keratinocytes, inhibition of the CK2 activity induced by 4,5,6,7-tetrabromobenzotriazole (TBB) causes reciprocal changes in the activities of major signal transduction regulators of keratinocytes differentiation, i.e. ERK1/2 and p38 MAPK, without affecting their protein levels. The ERK1/2 activity is strongly suppressed, while the activity of p38 is increased. We have also found that the activity of upstream and specifi c for p38 MAPK kinase MEK3/6 is also stimulated by TBB. These original results clearly demonstrate the participation of CK2 in the signal transduction pathway controlling MEK3/6, p38 MAPK, and ERK1/2 in the used model system.

scholarly journals HEMA Effects on Autophagy Mechanism in Human Dental Pulp Stem Cells

Materials ◽  
2019 ◽  
Vol 12 (14) ◽  
pp. 2285 ◽  
Author(s):  
Diomede ◽  
Tripodi ◽  
Trubiani ◽  
Pizzicannella
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Dental Pulp ◽  
Nuclear Translocation ◽  
Morphological Changes ◽  
Dental Pulp Stem Cells ◽  
Expression Levels ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Human Dental Pulp

Autophagy is a complex mechanism that permits the degradation of cellular components in order to enhance cell homeostasis, recycling the damaged, dysfunctional, or unnecessary components. In restorative dentistry practice, free resin monomers of 2-hydroxyethyl methacrylate (HEMA) can be released. The aim of this study was to investigate the effect of HEMA on proliferation and autophagy in human dental pulp stem cells (hDPSCs). Human DPSCs were treated with different concentrations of HEMA (3 and 5 mmol L−1). To evaluate the proliferation rate, MTT and trypan blue assays were used. Autophagic markers such as microtubule-associated protein 1 light chain 3 (LC3-I/II) and ubiquitin-binding protein (p62) were analyzed through immunofluorescence observations. Beclin1, LC3-I/II, and p62 were evaluated by means of Western blotting detection. Considering that activity of extracellular signal–regulated kinase (ERK) and its phosphorylated form (pERK) mediates several cellular processes, such as apoptosis, autophagy, and senescence, the involvement of ERK/pERK signaling was also evaluated. Obtained results showed a decreased cell proliferation associated with morphological changes in HEMA-treated cells. The Western blot results showed that the expression levels of Beclin1, LC3-I/II, and ERK were significantly elevated in HEMA-treated cells and in cells co-treated with rapamycin, an autophagic promoter. The expression levels of p62 were significantly reduced compared to the untreated samples. Protein levels to the autophagic process, observed at confocal microscopy confirmed the data obtained from the Western blot. The up-regulation of ERK and pERK levels, associated with nuclear translocation, revealed that ERK pathway signaling could act as a promoter of autophagy in dental pulp stem cells treated with HEMA.

scholarly journals MAPK Signal Transduction Pathway Regulation: A Novel Mechanism of Rat HSC-T6 Cell Apoptosis Induced by FUZHENGHUAYU Tablet

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Qi Wang ◽  
Hongbo Du ◽  
Min Li ◽  
Yue Li ◽  
Shunai Liu ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Target Genes ◽  
Stellate Cell ◽  
Signal Transduction Pathway ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Protein Levels ◽  
Control Serum ◽  
Pathway Regulation ◽  
Induced Apoptosis

FUZHENGHUAYU Tablets have been widely used in the treatment of liver fibrosis in China. Here, we investigate the apoptotic effect of FUZHENGHUAYU Tablet in rat liver stellate cell line HSC-T6. HSC-T6 cells were incubated with control serum or drug serum from rats fed with 0.9% NaCl or FUZHENGHUAYU Tablet, respectively. Cells exposed to drug serum showed higher proportions of early and late apoptotic cells than controls. The mRNA levels of collagens I and III, TGF-β1 andα-SMA were reduced by drug serum compared to control serum. Differentially expressed mRNAs and miRNAs were analyzed by microarray and sequencing, respectively. We identified 334 differentially expressed mRNAs and also 60 GOs and two pathways related to the mRNAs. Seventy-five differentially expressed miRNAs were down-regulated by drug serum and 1963 target genes were predicted. 134 GOs up-regulated in drug serum group were linked to miRNA targets, and drug serum also regulated 43 miRNA signal transduction pathways. Protein levels were evaluated by Western blot. Drug serum down-regulated (phospho-SAPK/JNK)/(SAPK/JNK) and up-regulated phospho-p38/p38 ratios. The study showed that FUZHENGHUAYU Tablet induced apoptosis in rat HSC-T6 cells possibly in part by activating p38 and inhibiting SAPK/JNK.

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