Gene expressions and enzyme analyses in theSchizosaccharomyces pombe Δpap1 transcription factor mutant exposed to Cd2+

Abstract Background and Aims Activating Transcription Factor 3 (ATF3) is a stress-adaptive transcription factor, which has been suggested to be involved in maintaining glucose homeostasis. ATF3 respond rapidly to various stimuli like high glucose, fatty acids and oxidative stress, and is observed to either protective or detrimental effects in diabetic condition. Therefore to elucidate the exact role in diabetic nephropathy of ATF3, we investigated the role of ATF3 by inhibition with Raf-inhibitor GW5047 on diabetic mice model. Method ATF3 level was examined in the mouse podocytes and NRK cells with either overexpression or downregulation with ATF3. 8 week db/m and db/db mice as the model of diabetic mice were examined for the expression of ATF3 and were treated with GW5074, a Raf1 kinase inhibitor targeting the ATF3 intraperitoneally with a dose of 0.5mg/kg for 12 weeks. Results In cultured mouse podocytes and NRK cells, high glucose and angiotensin II markedly increased ATF3 expression. Gene Expressions of NOX4, MCP-1 and NF-kB were augmented by ATF3, and were attenuated by ATF3 siRNA. In db/db mice, plasma ATF3 level was not different from control db/m, however the urinary ATF3 excretion was significantly higher. Treatment of GW5074 decreased urinary ATF3 excretion. After 12 week treatment, serum creatinine level was significantly lower in the treatment db/db group, with less systemic oxidative stress. There were no significant differences in body weight, whereas the food intake was decreased in GW5047 group. Overall lipid profile or HOMA-IR, HbA1c level was not different from each group. Serum adiponectin were otherwise increased in GW5074 group. Urinary excretion of albumin at 2 month of treatment decreased with urinary nephrin excretion. Trend of increased gene expression of JNK, p-38, smad2, ERK which was downregulated by GW5074 was noted. Conclusion These findings suggest that in diabetic condition, the activation of ATF3 is associated pathogenesis of diabetic nephropathy and targeting ATF3 may have a protective role in the disease progression.

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In Vitro Effects of Sodium Benzoate on the Expression of T Cells-related Cytokines and Transcription Factors in Adjuvant-induced Arthritis Model

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v19i(s1.r1).2853 ◽

2020 ◽

Author(s):

Peyman Bemani ◽

Zahra Amirghofran ◽

Eskandar Kamali-Sarvestani

Keyword(s):

T Cells ◽

Transcription Factor ◽

Transcription Factors ◽

Sodium Benzoate ◽

Ex Vivo ◽

Disease Process ◽

Gene Expressions ◽

Adjuvant Induced Arthritis ◽

Ifn Γ

Though the exact etiology of rheumatoid arthritis (RA) is unknown, the contribution of immune cells in the disease process is completely acknowledged. T helper (Th) 1 and Th17-related cytokines are required for the disease development and progression, while Th2 and regulatory T cells (Tregs)-derived cytokines are protective. Studies have shown that sodium benzoate (NaB) can switch the balance of Th cell subsets toward Th2 and Tregs. The present study aimed to evaluate the possible effects of NaB on the expression of CD4+T cells-related cytokines and transcription factors in splenocytes derived from an animal model of RA, adjuvant-induced arthritis (AIA). AIA was induced in rats by injection of Freund's adjuvant containing mycobacterial antigens (Mtb). Splenocytes were isolated from AIA rats and restimulated ex vivo with Mtb in the presence or absence of NaB for 24 h. To determine the effects of NaB on the expression of T cells-related cytokine and transcription factor genes, real-time PCR was performed. NaB treatment of Mtb-stimulated splenocytes derived from arthritic rats resulted in significant increases in the gene expressions of Tregs-related cytokines (IL-10 and TGF-β) and Foxp3 transcription factor, and significant decreases in the expression of Th1-related cytokines (TNF-α and IFN-γ) and the T-bet transcription factor. The ratios of Th1/Th2 (IFN-γ/IL-4), Th1/Treg (IFN-γ/TGF-β and IFN-γ/IL-10) and Th17/Treg (IL-17/IL-10 and IL-17/IL-10+TGF-β)-related cytokines were also significantly decreased. In conclusion, NaB can potentially be considered as a useful therapeutic agent for the treatment of RA and other Th1 and Th17-mediated diseases.

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Detection of deleted malignant brain tumors 1 and runt-related transcription factor 3 gene expressions in bladder carcinoma

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)71681-1 ◽

2008 ◽

Vol 6 (9) ◽

pp. 132

Author(s):

Y. Dodurga ◽

C. Biray Avci ◽

N.L. Satiroglu-Tufan ◽

C. Tataroglu ◽

Z. Kesen ◽

...

Keyword(s):

Transcription Factor ◽

Brain Tumors ◽

Bladder Carcinoma ◽

Gene Expressions ◽

Malignant Brain Tumors ◽

Related Transcription Factor ◽

Transcription Factor 3

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Evaluation of transcription factor and aquaporin gene expressions in response to Al2O3 and ZnO nanoparticles during barley germination

Plant Physiology and Biochemistry ◽

10.1016/j.plaphy.2021.06.018 ◽

2021 ◽

Author(s):

Hulya Akdemir

Keyword(s):

Transcription Factor ◽

Zno Nanoparticles ◽

Gene Expressions ◽

Aquaporin Gene

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Early activation of transcription factor NF-κB during ischemia in perfused rat heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.2.h543 ◽

1999 ◽

Vol 276 (2) ◽

pp. H543-H552 ◽

Cited By ~ 44

Author(s):

Chuanfu Li ◽

William Browder ◽

Race L. Kao

Keyword(s):

Transcription Factor ◽

Ischemia Reperfusion ◽

Immediate Early Gene ◽

Binding Activity ◽

Early Gene ◽

Immediate Early ◽

Pyrrolidine Dithiocarbamate ◽

Mrna Levels ◽

Gene Expressions ◽

Early Activation

The transcription factor nuclear factor κB (NF-κB) regulates multiple immediate-early gene expressions involved in immune and inflammatory responses and cellular defenses. Ischemia-reperfusion induces many immediate-early gene expressions, but little is known about the NF-κB activation in myocardium during ischemia and reperfusion. This study demonstrated that ischemia alone rapidly induced NF-κB activation in the myocardium of isolated working rat hearts. Electrophoretic mobility shift assay showed that NF-κB binding activity significantly increased in the nucleus after 5 min of ischemia and remained elevated for up to 30 min. Western blot analysis suggested that the levels of inhibitory IκBα protein in the cytoplasm became markedly decreased at 4, 5, 7.5, and 10 min of ischemia but were gradually restored following 10 min of ischemia. Reduction of IκBα protein in the cytoplasm by ischemia resulted in NF-κB translocation to the nucleus. Northern blot hybridization showed that IκBα mRNA levels were not significantly elevated during myocardial ischemia. Pyrrolidine dithiocarbamate, an antioxidant, significantly inhibited the loss of IκBα protein from the cytoplasm and prevented NF-κB binding activity in the nucleus. Reperfusion following short periods of ischemia augmented NF-κB binding activity in the nucleus induced by ischemia. The results suggest that early activation of NF-κB induced by ischemia in the myocardium could be a signal mechanism for controlling and regulating immediate-early gene expression during ischemia-reperfusion.

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Inhibition of kinase and endoribonuclease activity of ERN1/IRE1α affects expression of proliferationrelated genes in U87 glioma cells

Endoplasmic Reticulum Stress in Diseases ◽

10.1515/ersc-2015-0002 ◽

2015 ◽

Vol 2 (1) ◽

Cited By ~ 10

Author(s):

Oleksandr H. Minchenko ◽

Dariia O. Tsymbal ◽

Dmytro O. Minchenko ◽

Michel Moenner ◽

Olena V. Kovalevska ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Transcription Factor ◽

Endoplasmic Reticulum Stress ◽

Tumor Growth ◽

Mrna Level ◽

Glioma Cells ◽

Dominant Negative ◽

Fine Tuning ◽

Gene Expressions ◽

Endoribonuclease Activity

AbstractInhibition of ERN1/IRE1α (endoplasmic reticulum to nucleus signaling 1/inositol requiring enzyme-1α), the major signaling pathway of endoplasmic reticulum stress, significantly decreases tumor growth. We have studied the expression of transcription factors such as E2F8 (E2F transcription factor 8), EPAS1 (endothelial PAS domain protein 1), TBX3 (T-box 3), ATF3 (activating transcription factor 3), FOXF1 (forkhead box F1), and HOXC6 (homeobox C6) in U87 glioma cells overexpressing dominant-negative ERN1/IRE1α defective in endoribonuclease (dnr-ERN1) as well as defective in both kinase and endonuclease (dn-ERN1) activity of ERN1/IRE1α. We have demonstrated that the expression of all studied genes is decreased at the mRNA level in cells with modified ERN1/IRE1α; TBX3, however, is increased in these cells as compared to control glioma cells. Changes in protein levels of E2F8, HOXC6, ATF3, and TBX3 corresponded to changes in mRNAs levels. We also found that two mutated ERN1/IRE1α have differential effects on the expression of studied transcripts. The presence of kinase and endonuclease deficient ERN1/IRE1α in glioma cells had a less profound effect on the expression of E2F8, HOXC6, and TBX3 genes than the blockade of the endoribonuclease activity of ERN1/IRE1α alone. Kinase and endonuclease deficient ERN1/IRE1α suppresses ATF3 and FOXF1 gene expressions, while inhibition of only endoribonuclease of ERN1/IRE1α leads to the up-regulation of these gene transcripts. The present study demonstrates that fine-tuning of the expression of proliferation related genes is regulated by ERN1/IRE1α an effector of endoplasmic reticulum stress. Inhibition of ERN1/IRE1α, especially its endoribonuclease activity, correlates with deregulation of proliferation related genes and thus slower tumor growth.

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Macrophage-specific IRF5 deficiency stabilizes atherosclerotic plaques in ApoE−/− mice

European Heart Journal ◽

10.1093/ehjci/ehaa946.3748 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I Hilgendorf ◽

C Haerdtner ◽

J Leipner ◽

B Dufner ◽

N Hoppe ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Transcription Factor ◽

Atherosclerotic Plaque ◽

Macrophage Polarization ◽

High Cholesterol Diet ◽

Funding Source ◽

Gene Expressions ◽

M1 Macrophage

Abstract Background Interferon regulatory factor (IRF) 5 is a transcription factor promoting inflammatory macrophage polarization (M1 type). Given the central role of macrophages in atherosclerotic plaque development we hypothesized that macrophage specific deletion of IRF5 will protect from atherosclerosis. Purpose Investigate whether intrinsic blockade of M1 macrophage polarization ameliorates atherosclerosis Methods Female ApoE−/−LysMCre/wtIRF5flox/floxand ApoE−/−LysMwt/wtIRF5flox/floxmice were fed a high cholesterol diet for 3 months, and atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependend bone marrow derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Aortic macrophage chimerism in irradiated ApoE−/− mice reconstituted with a mixture of CD45.1+ ApoE−/− (WT) and CD45.2+ ApoE−/− LysMCre/WtIRF5flox/flox(KO) bone marrow was evaluated to distinguish systemic from intra-plaque effects on monocyte/macrophage kinetics. Results Macrophage-specific IRF5 deficiency blunted LPS/IFNg-induced IL-1β and TNFα gene expression in vitro. In ApoE−/− mice, macrophage-specific IRF5 deficiency did not alter lesion size in the aortic root but significantly reduced macrophage and lipid contents by about 25% while increasing collagen deposition by over 30%. This was accompanied by relative reductions in gene expressions of pro-inflammatory (IL-1β, IL-6, IL-12) and increases in anti-inflammatory (Mertk, TGFβ, CD206) markers in atherosclerotic aortas of ApoE−/−LysMCre/wtIRF5flox/floxmice. When competing with IRF5 deficient cells in mixed irradiation bone marrow chimeras, IRF5 competent macrophages showed an advantage in accumulating in atherosclerotic aortas as disease progressed independent of monocyte recruitment. Conclusion Transcription factor IRF5 promotes a pro-inflammatory response in macrophages leading to vulnerable plaque formation and plaque destabilization, providing genetic evidence for targeting macrophage polarization in atherosclerosis. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): DFG

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Transcription Factor Oscillations Induce Differential Gene Expressions

Biophysical Journal ◽

10.1016/j.bpj.2012.04.023 ◽

2012 ◽

Vol 102 (11) ◽

pp. 2413-2423 ◽

Cited By ~ 18

Author(s):

Keng Boon Wee ◽

Wee Kheng Yio ◽

Uttam Surana ◽

Keng Hwee Chiam

Keyword(s):

Transcription Factor ◽

Gene Expressions ◽

Differential Gene

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X-box-binding protein 1 is required for pancreatic development in Xenopus laevis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa114 ◽

2020 ◽

Vol 52 (11) ◽

pp. 1215-1226

Author(s):

Jing Yang ◽

Xingjing Liu ◽

Fang Yuan ◽

Jia Liu ◽

Deli Li ◽

...

Keyword(s):

Transcription Factor ◽

Xenopus Laevis ◽

Binding Protein ◽

Exocrine Function ◽

Marker Genes ◽

Gene Expressions ◽

Pancreatic Development ◽

Expression Levels ◽

Pancreatic Exocrine

Abstract X-box-binding protein 1 (XBP1) is a protein containing the basic leucine zipper structure. It belongs to the cAMP-response element binding protein (CREB)/activating transcription factor transcription factor family. As the main transcription factor, spliced XBP1 (XBP1s) participates in many physiological and pathological processes and plays an important role in embryonic development. Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency, indicating that XBP1 plays an important role in pancreatic development. However, the exact role of XBP1 in pancreatic development remains unclear. This study aimed to investigate the role of XBP1 in the pancreatic development of Xenopus laevis embryos. Whole-mount in situ hybridization and quantitative real-time PCR results revealed that the expression levels of pancreatic progenitor marker genes pdx1, p48, ngn3, and sox9 were downregulated in XBP1s morpholino oligonucleotide (MO)-injected embryos. The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated. Through the overexpression of XBP1s, the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos. Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter. These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.

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