The activation of transcription factor NF-kappaB (nuclear factor-kappaB) plays a central role in the induction of many inflammatory response genes. This process is characterized by either oscillations or stable induction of NF-kappaB nuclear binding. Changes in dynamics of binding result in the expression of distinct subsets of genes leading to different physiological outcomes. We examined NF-kappaB DNA binding activity in lipopolysaccharide (LPS)-stimulated IC-21 cells by electromobility shift assay and nonradioactive transcription factor assay and interpreted the results using a kinetic model of NF-kappaB activation. Both assays detected damped oscillatory behavior of NF-kappaB with differences in sensitivity and reproducibility. 3,4-Dichloropropionaniline (DCPA) was used to modulate the oscillatory behavior of NF-kappaB after LPS stimulation. DCPA is known to inhibit the production of two NF-kappaB-inducible cytokines, IL-6 and tumor necrosis factor alpha, by reducing but not completely abrogating NF-kappaB-induced transcription. DCPA treatment resulted in a potentiation of early LPS-induced NF-kappaB activation. The nonradioactive transcription factor assay, which has a higher signal/noise ratio than the electromobility shift assay, combined with in silico modeling, produced results that revealed changes in NF-kappaB dynamics which, to the best of our knowledge, have never been previously reported. These results highlight the importance of cell type and stimulus specificity in transcription factor activity assessment. In addition, assay selection has important implications for network inference and drug discovery.
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http://dx.doi.org/10.1529/biophysj.107.120451 | DOI Listing |
Mol Med Rep
March 2025
Department of Orthopedics, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, P.R. China.
Osteoarthritis (OA) is a common joint disorder involving the cartilage and other joint tissues. Quercetin (QCT) serves a protective role in the development of OA. However, to the best of our knowledge, the regulatory mechanisms of QCT in the progression of OA have not yet been fully elucidated.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Anqing Medical College Clinical Research Center, Anqing Municipal Hospital, Anqing, Anhui, P.R. China.
Our previous research identified that lncRNA PVT1 is upregulated in patients with IA. However, the precise functions of PVT1 in IA remain unclear. We compared the levels of PVT1, caspase-3, caspase-1, and NLRP3 in normal and IA patients.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Anorectal, Affiliated Hospital of Jiaxing University, The Second Hospital of Jiaxing, Jiaxing City, Zhejiang Province, China.
The underlying regulating mechanisms of miR-105-5p/PTEN in colon cancer (CC) progression are still unknown. MiR-105-5p and PTEN expressions were determined using RT-PCR. PTEN protein levels were examined by western blot.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Microscopic and Developmental Anatomy, Tokyo Women's Medical University, Tokyo, Japan.
Most blood cells derive from hematopoietic stem cells (HSCs), originating from endothelial cells. The induction of HSCs from endothelial cells occurs during mid-gestation, and research has revealed multiple steps in this induction process. Hemogenic endothelial cells emerge within the endothelium, transition to hematopoietic cells (pre-HSCs), and subsequently mature into functional HSCs.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. The heterogeneity of the tumor microenvironment significantly influences patient prognosis, while the diversity of tumor cells shapes its unique characteristics. A comprehensive analysis of the molecular profile of tumor cells is crucial for identifying novel molecular targets for drug sensitivity analysis and for uncovering the pathophysiological mechanisms underlying CRC.
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