A biphasic role of nuclear transcription factor (NF)-κB in the islet β-cell apoptosis induced by interleukin (IL)-1β

2005 ◽  
Vol 204 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Gianpaolo Papaccio ◽  
Antonio Graziano ◽  
Riccardo d'Aquino ◽  
Salvatore Valiante ◽  
Fabio Naro
Keyword(s):  
Transcription Factor ◽  
Cell Apoptosis ◽  
Β Cell ◽  
Nuclear Transcription Factor

scholarly journals Deficiency of VCP-Interacting Membrane Selenoprotein (VIMP) Leads to G1 Cell Cycle Arrest and Cell Death in MIN6 Insulinoma Cells

2018 ◽  
Vol 51 (5) ◽  
pp. 2185-2197 ◽  
Author(s):  
Lili Men ◽  
Juan Sun ◽  
Decheng Ren
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Insulin Secretion ◽  
Cell Apoptosis ◽  
Β Cells ◽  
Β Cell ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Insulinoma Cells

Background/Aims: VCP-interacting membrane selenoprotein (VIMP), an ER resident selenoprotein, is highly expressed in β-cells, however, the role of VIMP in β-cells has not been characterized. In this study, we studied the relationship between VIMP deficiency and β-cell survival in MIN6 insulinoma cells. Methods: To determine the role of VIMP in β-cells, lentiviral VIMP shRNAs were used to knock down (KD) expression of VIMP in MIN6 cells. Cell death was quantified by propidium iodide (PI) staining followed by flow cytometric analyses using a FACS Caliber and FlowJo software. Cell apoptosis and proliferation were determined by TUNEL assay and Ki67 staining, respectively. Cell cycle was analyzed after PI staining. Results: The results show that 1) VIMP suppression induces β-cell apoptosis, which is associated with a decrease in Bcl-xL, and the β-cell apoptosis induced by VIMP suppression can be inhibited by overexpression of Bcl-xL; 2) VIMP knockdown (KD) decreases cell proliferation and G1 cell cycle arrest by accumulating p27 and decreasing E2F1; 3) VIMP KD suppresses unfolded protein response (UPR) activation by regulating the IRE1α and PERK pathways; 4) VIMP KD increases insulin secretion. Conclusion: These results suggest that VIMP may function as a novel regulator to modulate β-cell survival, proliferation, cell cycle, UPR and insulin secretion in MIN6 cells.

scholarly journals Down Regulation of SIRT2 Reduced ASS Induced NSCLC Apoptosis Through the Release of Autophagy Components via Exosomes

2020 ◽  
Vol 8 ◽  
Author(s):  
Lei Wang ◽  
Pei Xu ◽  
Xiao Xie ◽  
Fengqing Hu ◽  
Lianyong Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Nsclc Cell ◽  
Dependent Manner ◽  
Cell Metastasis ◽  
Rna Immunoprecipitation ◽  
Transcription Factor Eb

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3′UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.

scholarly journals The role of suppressor of cytokine signaling SOCS7 in the regulation of the phosphorylation of inhibitor of nuclear transcription factor NF-KB in mononuclear leukocytes and production of cytokines in community-acquired bacterial pneumonia

2018 ◽  
pp. 138-140
Author(s):  
S. S. Bondar ◽  
I. V. Terekhov ◽  
V. S. Nikiforov ◽  
V. K. Parfenyuk ◽  
N. V. Bondar
Keyword(s):  
Transcription Factor ◽  
Linear Regression Analysis ◽  
Negative Relationship ◽  
Adaptive Immune Response ◽  
Community Acquired Pneumonia ◽  
Cytokine Signaling ◽  
Mononuclear Leukocytes ◽  
Nuclear Transcription Factor ◽  
Factor Inhibitor

The study discusses the relationship between the content of NF-KB and cytokine signaling suppressor 7 (SOCS7) in mononuclear peripheral blood cells (MNC) phosphorylated form of nuclear transcription factor inhibitor (NF-KB) and the production of MNC cytokines (TNF, IFN, IL-1β, IL-4, IL-10, IL-12) determining the state of congenital and adaptive immune response.The content and level of phosphorylation of the nuclear transcription factor NF-KB (Ikba) inhibitor and the SOCS7 protein concentration were determined by enzyme immunoassay in MNC. In addition, the concentration of TNF, IFN, IL-1β, IL-4, IL-10, IL-12 was determined in cellular supernatants. The interrelations between the studied factors were evaluated by the method of linear regression analysis.The results of the study indicate that the stage of recovery of community-acquired pneumonia is accompanied by a decrease in the level of IL-1, TNF and IL-4 and an increase in the production of Information. Also in the stage of convalescence there is a decrease in phosphorylation of Ikba and an increase in the concentration of SOCS7 in the OLS. The analysis revealed a significant effect on the level of phosphorylation of Ikba content in the cell SOCS7. Thus, a strong negative relationship between SOCS7 and phosphorylation of Ikba can be mediated by inhibition under its influence of STAT3/5 and MARK / SAPK-dependent cytokine production mechanisms, which allows to consider this factor as a therapeutic target for limiting excessive immunosuppression in pneumonia.

A novel secretagogin/ATF4 pathway is involved in oxidized LDL-induced endoplasmic reticulum stress and islet β-cell apoptosis

2020 ◽  
Author(s):  
Li Wu ◽  
Yuncheng Lv ◽  
Ying Lv ◽  
Sunmin Xiang ◽  
Zhibo Zhao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Cell Apoptosis ◽  
Initiation Factor ◽  
Β Cells ◽  
Β Cell ◽  
Immunoprecipitation Assay ◽  
Min6 Cells ◽  
Stress Markers

Abstract Excessive accumulation of cholesterol in β cells initiates endoplasmic reticulum (ER) stress and associated apoptosis. We have reported that excessive uptake of cholesterol by MIN6 cells decreases the expression of secretagogin (SCGN) and then attenuates insulin secretion. Here, we aimed to determine whether cholesterol-induced SCGN decrease is involved in the modulation of ER stress and apoptosis in pancreatic β cells. In this study, MIN6 cells were treated with oxidized low-density lipoprotein (ox-LDL) for 24 h, and then intracellular lipid droplets and cell apoptosis were quantified, and SCGN and ER stress markers were identified by western blot analysis. Furthermore, small interfer RNA (siRNA)-mediated SCGN knockdown and recombinant plasmid-mediated SCGN restoration experiments were performed to confirm the role of SCGN in ER stress and associated cell apoptosis. Finally, the interaction of SCGN with ATF4 was computationally predicted and then validated by a co-immunoprecipitation assay. We found that ox-LDL treatment increased the levels of ER stress markers, such as phosphorylated protein kinase-like endoplasmic reticulum kinase, phosphorylated eukaryotic initiation factor 2 alpha, activating transcription factor 4 (ATF4), and transcription factor CCAAT-enhancer-binding protein homologous protein, and promoted MIN6 cell apoptosis; in addition, the expression of SCGN was downregulated. siRNA-mediated SCGN knockdown exacerbated β-cell ER stress by increasing ATF4 expression. Pretreatment of MIN6 cells with the recombinant SCGN partly antagonized ox-LDL-induced ER stress and apoptosis. Furthermore, a co-immunoprecipitation assay revealed an interaction between SCGN and ATF4 in MIN6 cells. Taken together, these results demonstrated that pancreatic β-cell apoptosis induced by ox-LDL treatment can be attributed, in part, to an SCGN/ATF4-dependent ER stress response.

Strain response in fibroblasts indicates a possible role of the Ca2+-dependent nuclear transcription factor NM1 in RNA synthesis

Cell Calcium ◽  
2011 ◽  
Vol 49 (4) ◽  
pp. 259-271 ◽  
Author(s):  
Thorsten Steinberg ◽  
Nelli Ziegler ◽  
Angel Alonso ◽  
Annette Kohl ◽  
Eva Müssig ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Synthesis ◽  
Strain Response ◽  
Nuclear Transcription Factor

scholarly journals Role for Activating Transcription Factor 3 in Stress-Induced β-Cell Apoptosis

2004 ◽  
Vol 24 (13) ◽  
pp. 5721-5732 ◽  
Author(s):  
Matthew G. Hartman ◽  
Dan Lu ◽  
Mi-Lyang Kim ◽  
Gary J. Kociba ◽  
Tala Shukri ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Cell Apoptosis ◽  
Activating Transcription Factor 3 ◽  
Β Cells ◽  
Β Cell ◽  
Activating Transcription Factor

ABSTRACT Activating transcription factor 3 (ATF3) is a stress-inducible gene and encodes a member of the ATF/CREB family of transcription factors. However, the physiological significance of ATF3 induction by stress signals is not clear. In this report, we describe several lines of evidence supporting a role of ATF3 in stress-induced β-cell apoptosis. First, ATF3 is induced in β cells by signals relevant to β-cell destruction: proinflammatory cytokines, nitric oxide, and high concentrations of glucose and palmitate. Second, induction of ATF3 is mediated in part by the NF-κB and Jun N-terminal kinase/stress-activated protein kinase signaling pathways, two stress-induced pathways implicated in both type 1 and type 2 diabetes. Third, transgenic mice expressing ATF3 in β cells develop abnormal islets and defects secondary to β-cell deficiency. Fourth, ATF3 knockout islets are partially protected from cytokine- or nitric oxide-induced apoptosis. Fifth, ATF3 is expressed in the islets of patients with type 1 or type 2 diabetes, and in the islets of nonobese diabetic mice that have developed insulitis or diabetes. Taken together, our results suggest ATF3 to be a novel regulator of stress-induced β-cell apoptosis.

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